SEARCH · PubMed Health

Results for “polymorphisms”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources

PubMed2002

Polymorphism of renin-angiotensin system genes in dialysis patients--association with cerebrovascular disease.

BACKGROUND: Polymorphisms of genes of the renin-angiotensin system (RAS) have been found in association with cerebrovascular and cardiovascular diseases in the general population. In dialysis patients, RAS gene polymorphisms have been studied in combination and separately and have yielded conflicting results. METHODS: In this study we have analysed, in 160 dialysis patients, the distribution of the following genetic polymorphisms: M235T and T174M of the angiotensinogen gene, A1166C of the angiotensin II type 1 receptor gene and the insertion/deletion (I/D) of the ACE gene. The association of these polymorphisms with cerebrovascular and cardiovascular diseases was also tested. Healthy blood donors and hospital staff (169) were the control group for the distribution of the polymorphisms. RESULTS: The distribution of the polymorphisms in dialysis patients as a whole did not differ significantly from that of healthy controls. However, for patients with severe cerebrovascular disease, 70% carried the D allele compared with 52% of patients without cerebrovascular disease (P=0.035). We also found that the degree of carotid artery stenosis was significantly correlated with the presence of the ACE 'D' allele in subjects on dialysis (P=0.0348). CONCLUSIONS: The distribution of RAS genes in dialysis patients is similar to that of the normal population. The presence of the D allele of ACE gene is associated with cerebrovascular disease and the degree of carotid artery stenosis. We postulate that the ACE gene polymorphism is a risk factor for cerebrovascular disease in dialytic patients.

Aged↗

PubMed2003

Effects of the C677T and A1298C polymorphisms of the MTHFR gene on the genetic predisposition for diabetic nephropathy.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme of homocysteine metabolism. The C677T polymorphism of the MTHFR gene has been reported to be associated with elevated plasma homocysteine in patients with low folic acid intake. A recently reported second common polymorphism, A1298C, may increase homocysteine, but only in individuals carrying the T677 allele. This study aimed to investigate the influence of the C677T and A1298C polymorphisms of the MTHFR gene on the development of diabetic nephropathy in Caucasian patients with type 2 diabetes. METHODS: We genotyped 429 type 2 diabetic patients for the C677T and A1298C polymorphisms using standard PCR-based protocols, and divided them into three groups based on renal status: 159 patients with normoalbuminuria, 149 with microalbuminuria, and 121 with persistent proteinuria and chronic renal failure (CRF). The C677T and A1298C genotype frequencies were compared among the three groups. RESULTS: Although the frequencies of the CT and TT genotypes of the C677T polymorphism tended to increase with each stage of diabetic nephropathy (53, 56 and 63% in normoalbuminuria, microalbuminuria and proteinuria/CRF, respectively), these differences were not significant. When male and female patients were analysed separately, the effect was seen only in males. The CT + TT genotype was present in 46% of male patients with normoalbuminuria, in 57% with microalbuminuria and in 68% with proteinuria/CRF (OR = 2.46; 95% CI 1.13-5.38). There were no differ-ences in the A1298C polymorphism among the three groups. CONCLUSIONS: These findings indicate that the C677T polymorphism is a risk factor for diabetic nephrop-athy in male patients with type 2 diabetes.

Aged↗

PubMedDate not supplied

Formation of nucleolar polymorphisms in trisomic chickens and subsequent microevolution of rRNA gene clusters in diploids.

Variations in nucleolar size are common in animals and man, yet the basis and significance of this variation are not well understood. In this report, we describe the generation de novo of individuals that express nucleolar size variations (polymorphisms) and the underlying basis for this phenotype in a vertebrate animal system (Gallus domesticus). Individuals that express nucleolar size polymorphisms were produced from mating chickens trisomic for the nucleolar organizer (NO) chromosome; 10%-18% of progeny demonstrated nucleolar polymorphisms. These progeny were incorporated into a diploid genetic line in which the polymorphic trait was observed to segregate in Mendelian fashion. An even more dramatic nucleolar size polymorphism (one macro- plus one micronucleolus) evolved in one diploid family over the course of only two generations. These individuals were used to ascertain that the polymorphic-nucleoli phenotype was expressed in tissues derived from the three primary embryonic cell layers in embryos and neonates. Image analysis was conducted on cells of these birds to quantitate the size differences between macro- and micronucleoli (5 mu2 versus 1 mu2, respectively). Finally, these birds were studied with the technique of in situ hybridization, which showed that gene number differences between homologous NO chromosomes (i.e., heterozygosity for rRNA gene copy number), underlies the polymorphic-nucleoli phenotype. Thus, the chicken emerges as an experimental system through which heterozygosity for the rRNA gene copy number can be induced, easily identified, transmitted, and expressed in all somatic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Lack of geographic variation in anonymous nuclear polymorphisms in the American oyster, Crassostrea virginica.

Comparing geographic variation of noncoding nuclear DNA polymorphisms, which presumably are neutral to natural selection, with geographic variation of allozymes is potentially a good way to detect the effects of selection on allozyme polymorphisms. A previous study of four anonymous nuclear markers in the American oyster, Crassostrea virginica, found dramatic differences in allele frequency between the Gulf of Mexico and the Atlantic Ocean. In contrast, 14 allozyme polymorphisms were fairly uniform in frequency between the two areas. This led to the conclusion that all of the allozyme polymorphisms were kept uniform in frequency by balancing selection. To test the robustness of this pattern, six additional anonymous nuclear DNA polymorphisms were surveyed in oysters from Panacea, Fla, and Charleston, S.C. on the Gulf and Atlantic coasts, respectively. Unlike the previously studied DNA markers, the six DNA polymorphisms examined here show geographic variation that is not significantly greater than that of allozymes. The reason for the discrepancy between the two sets of DNA polymorphisms is unclear.

Alleles↗

PubMed1997

Persistent nuclear ribosomal DNA sequence polymorphism in the Amelanchier agamic complex (Rosaceae).

Individual plants of several Amelanchier taxa contain many polymorphic nucleotide sites in the internal transcribed spacers (ITS) of nuclear ribosomal DNA (nrDNA). This polymorphism is unusual because it is not recent in origin and thus has resisted homogenization by concerted evolution. Amelanchier ITS sequence polymorphism is hypothesized to be the result of gene flow between two major North American clades resolved by phylogenetic analysis of ITS sequences. Western North American species plus A. humilis and A. sanguinea of eastern North America form one clade (A), and the remaining eastern North American Amelanchier make up clade B. Five eastern North American taxa are polymorphic at many of the nucleotide sites where clades A and B have diverged and are thought to be of hybrid origin, with A. humilis or A. sanguinea as one parent and various members of clade B as the other parent. Morphological evidence suggests that A. humilis is one of the parents of one of the polymorphic taxa, a microspecies that we refer to informally as A. "erecta." Sequences of 21 cloned copies of the ITS1-5.8S gene-ITS2 region from one A. "erecta" individual are identical to A. humilis sequence or to the clade B consensus sequence, or they are apparent recombinants of A. humilis and clade B ITS repeats. Amelanchier "erecta" and another polymorphic taxon are suspected to be relatively old because both grow several hundred kilometers beyond the range of one of their parents. ITS sequence polymorphisms have apparently persisted in these two taxa perhaps because of polyploidy and/or agamospermy (asexual seed production), which are prevalent in the genus.

Base Sequence↗

PubMed1998

Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence.

The neutral theory of molecular evolution predicts that the ratio of polymorphisms to fixed differences should be fairly uniform across a region of DNA sequence. Significant heterogeneity in this ratio can indicate the effects of balancing selection, selective sweeps, mildly deleterious mutations, or background selection. Comparing an observed heterogeneity statistic with simulations of the heterogeneity resulting from random phylogenetic and sampling variation provides a test of the statistical significance of the observed pattern. When simulated data sets containing heterogeneity in the polymorphism-to-divergence ratio are examined, different statistics are most powerful for detecting different patterns of heterogeneity. The number of runs is most powerful for detecting patterns containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic is most powerful for detecting patterns in which one end of the gene has high polymorphism and the other end has low polymorphism; and a newly developed statistic, the mean sliding G statistic, is most powerful for detecting patterns containing one or two peaks of polymorphism with reduced polymorphism on either side. Nine out of 27 genes from the Drosophila melanogaster subgroup exhibit heterogeneity that is significant under at least one of these three tests, with five of the nine remaining significant after a correction for multiple comparisons, suggesting that detectable evidence for the effects of some kind of selection is fairly common.

Animals↗

PubMed2000

High DNA sequence variability at the alpha 1 Na/K-ATPase locus of Artemia franciscana (brine shrimp): polymorphism in a gene for salt-resistance in a salt-resistant organism.

We previously reported that the Na/K-ATPase alpha 1 subunit coding gene showed signs of being a very polymorphic locus in Artemia franciscana. This species is adapted to highly saline waters, and the Na/K-ATPase alpha 1 isoform presumably plays a key role in this adaptation. Therefore, we were interested in further study of the alpha 1 Na/K-ATPase polymorphisms to examine whether they might be due to an adaptation to salt resistance driven by natural selection. Using coding sequences from 10 genomic clones and 3 cDNAs, we observed that most substitutions are in synonymous positions (88.8%). The 12 nonsynonymous substitutions code for conservative amino acid replacements with an apparent scattered distribution across functional domains of the protein. Interspecific comparison between these sequences and two genomic clones from Artemia parthenogenetica containing 1,122 bp of the alpha 1 Na/K-ATPase locus coding sequence showed independence of the synonymous/nonsynonymous ratio in the comparison within A. franciscana and between A. franciscana and A. parthenogenetica, which fits the neutral model of evolution. Since there were no previous studies on DNA polymorphism for other A. franciscana genes, we also studied variability at the Actin 302 locus for comparison. Both loci were amplified by reverse transcription-polymerase chain reaction, and 20 sequences were obtained for each. This study shows that the amplified region of the alpha 1 Na/K-ATPase gene is 3.5 times as polymorphic as the Actin 302 gene and 2.9 times as heterozygotic. Interestingly, under a model of neutral evolution, the data observed would be expected with a probability of approximately 0.05, suggesting an excess of intraspecific variation of alpha 1 Na/K-ATPase with respect to Actin 302. Restriction fragment length polymorphism studies show similar patterns of polymorphism along the approximately 41-kb span of the alpha 1 Na/K-ATPase locus. Most of the nucleotide differences are linked in a few haplotypes, although recombination events are also inferred from the data. We propose a possible explanation for the high polymorphic levels at the alpha 1 Na/K-ATPase locus which invokes positive selection acting tightly to the locus in transiently isolated or semi-isolated subpopulations.

Actins↗

PubMed2005

Preprohypocretin polymorphisms in Parkinson disease patients reporting "sleep attacks".

STUDY OBJECTIVES: Previously, we found a significant association between the dopamine D2 receptor gene polymorphism Taq IA and sudden onset of sleep in patients with Parkinson disease. Here we evaluated the association between the preprohypocretin (-909T/C), (-22C/T), and (-20C/A) polymorphisms and sudden onset of sleep in the same population of patients with Parkinson disease. DESIGN: We conducted an association study analyzing the distribution of preprohypocretin polymorphisms in Germanic, caucasian Parkinson disease patients with and without sudden onset of sleep, matched according to drug therapy, disease duration, sex, and age. SETTING: Movement disorders section at a university hospital. PARTICIPANTS: 132 Parkinson disease patients with sudden onset of sleep and 132 Parkinson disease patients without sudden onset of sleep. INTERVENTIONS: Blood samples were taken from each participant and used for DNA extraction. Polymorphisms were analyzed by established polymerase chain reaction protocols or direct sequencing. MEASUREMENTS AND RESULTS: The variant allele T of the (-909T/C) preprohypocretin polymorphism was more commonly found in Parkinson disease patients with sudden onset of sleep. Statistical analysis showed that there were significant differences in the genotype (P = .024) and allele (P = .018) distribution between both groups. For heterozygous and homozygous carriers of allele T, the genotype relative-risk estimates for the presence of sudden onset of sleep were 2.01 (95% confidence interval: 0.76-5.34) and 2.81 (95% confidence interval: 1.09-7.25), respectively. CONCLUSIONS: Our results show a significant association between the (-909T/C) preprohypocretin polymorphism and sudden onset of sleep in Parkinson disease. However, we could not demonstrate any interaction between the Taq IA and (-909T/C) polymorphisms with respect to the occurrence of sudden onset of sleep, suggesting that multiple genetic factors may contribute to the pathogenesis of this phenomenon.

Alleles↗

PubMed2005

Variability in human sensitivity to 1,3-butadiene: influence of polymorphisms in the 5'-flanking region of the microsomal epoxide hydrolase gene (EPHX1).

The carcinogenic effects of 1,3-butadiene (BD), a mutagenic chemical widely used in the manufacture of synthetic rubber, are likely initiated through its epoxide metabolites. In humans, these epoxides are detoxified predominantly by hydrolysis, a reaction mediated by the microsomal epoxide hydrolase (mEH; EPHX1) enzyme. It appears reasonable to hypothesize that BD-exposed individuals possessing lower mEH detoxification capacity may have elevated risk of adverse health effects. The interindividual levels of mEH enzymatic activity vary considerably, and polymorphisms in the mEH gene may contribute to this variability. In addition to the well-studied coding region polymorphisms encoding Tyr113His and His139Arg substitutions, seven other polymorphic sites in the 5'-flanking region of the mEH gene have been reported. These polymorphisms appear to differentially affect mEH gene transcriptional activities. The 5'-flanking region polymorphisms exist in two linkages, the -200 linkage (-200C/T, -259C/T, -290T/G) and the -600 linkage (-362A/G, -613T/C, -699T/C), whereas the -399T/C polymorphism exists as an independent site. Because these polymorphisms may affect total mEH enzymatic activity, we hypothesized that they influence the mutagenic response associated with occupational exposure to BD. We genotyped the 5'-region of the mEH gene in 49 non-smoking workers from two styrene-butadiene rubber facilities in southeast Texas and evaluated the linkage patterns against results obtained from an autoradiographic HPRT mutant lymphocyte assay, used as a biomarker of genotoxic effect. In the study population, 67% were exposed to low BD levels, <150 parts per billion, and 33% were exposed to >150 ppb. We used the observed HPRT mutant (variant) frequency (VF) in the studied population and a 4-way first-order interaction statistical model to estimate parameters that describe the influence of exposure, genotypes and the interaction between the two on the HPRT VF in the target population. The background (baseline) VF, defined as the VF (x 10(-6)) +/- S.E.M. at low levels of BD exposure (<150 ppb) where all the genotypes under study are homozygous wild-type, was estimated to be 4.02 +/- 1.32. Exposure to >150 ppb of BD alone resulted in an estimated increase in VF of 3.42 +/- 2.47 above the baseline level. Inheritance of the variant ATT allele in the -600 linkages resulted in an estimated increase in VF of 3.39 +/- 1.67 above the baseline level. When the interaction between BD exposure and the ATT allele in the -600 linkage group was considered, a statistically significant positive interaction was observed, with an estimated increase in the VF of 10.89 +/- 2.16 (95% CI = 6.56-15.20; p = 0.0027) above baseline. These new data confirm and extend our previous findings that sensitivity to the genotoxic effects of BD is inversely correlated with predicted mEH activity.

5' Flanking Region↗

PubMed1999

Analysis of two human leukocyte antigen-linked polymorphic heat shock protein 70 genes in patients with severe sepsis.

OBJECTIVE: To determine whether the genotype and allelic frequencies of two human leukocyte antigen-linked bi-allelic 70-kilodalton heat shock protein (HSP70) gene polymorphisms are associated with susceptibility to and outcome of severe sepsis. Furthermore, we investigated a possible linkage between HSP70 gene polymorphisms and the previously reported and mortality-related tumor necrosis factor-beta (TNF-beta) NcoI gene polymorphism. DESIGN: Consecutive entry study of patients with severe sepsis. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Eighty-seven patients with a diagnosis of severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied two bi-allelic polymorphisms within the coding region of the constitutively expressed HSP70-HOM C/T, and the stress-inducible HSP70-2 G/A in patients with severe sepsis. The HSP70-HOM Ncol, HSP70-2 Pstl, and TNF-beta NcoI polymorphisms were identified by means of the polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. No significant differences in genotype and allelic frequencies were observed for both HSP70 gene polymorphisms between the 87 patients and the 110 healthy Caucasians serving as the control group. In addition, no differences in genotype and allelic frequencies between surviving and nonsurviving patients were detected. The allelic frequencies in the group of nonsurvivors were 0.8 for the HSP70-HOM C allele and 0.2 for the HSP70-HOM T allele vs. 0.87 and 0.13 for the survivors (p > .05). The frequency for the HSP70-2 G allele was 0.36 and 0.64 for the HSP70-2 A allele in the group of nonsurvivors vs. 0.41 and 0.59 for the survivors (p > .05). Analysis of a possible linkage between HSP70 and TNF-beta genotypes resulted in a significant association (odds ratio, 4.15; p < .01) of the HSP70-2 A/A homozygous genotype and the TNFB2/B2 homozygous genotype, which is reported to be a genomic marker for a poor prognosis in severe sepsis. CONCLUSIONS: Our data show that the bi-allelic NcoI and PstI polymorphisms within the HSP70-HOM and HSP70-2 locus, respectively, are associated with neither susceptibility to nor outcome of severe sepsis. Moreover, we found a linkage between HSP70-2 A homozygotes and the previously reported and mortality-related homozygous genotype, TNFB2/B2, in patients suffering from severe sepsis.

Case-Control Studies↗

PubMed2002

alpha-Adducin Gly460Trp polymorphism, left ventricular mass and plasma renin activity.

OBJECTIVE: Left ventricular hypertrophy (LVH) is associated with an increased risk for cardiovascular morbidity and mortality. Epidemiological studies suggest that LVH may be influenced by genetic factors. However, the evidence associating individual genes with left ventricular (LV) mass is inconsistent and contradictory. METHODS: We investigated the association between angiotensin-converting enzyme insertion/deletion, angiotensinogen and alpha-adducin polymorphisms with LV mass and plasma renin activity (PRA) in 162 men with mild, never-treated hypertension who were recruited for the Hypertension and Ambulatory Recording Venetia Study. The effect of each polymorphism on LV mass and PRA was tested in one-way analysis of covariance using LV mass index or PRA as the dependent variable after adjusting for covariates. RESULTS: The alpha-adducin polymorphism was the only individual polymorphism independently associated with LV mass index (F = 7.78, P= 0.006). Patients homozygous for the allele of that polymorphism had a LV mass index (123.4 +/- 10.5 g/m(2) ) significantly higher compared with heterozygotes (90.8 +/- 2.5 g/m(2) , P<0.01) or homozygotes (94.7 +/- 1.7 g/m(2) , P<0.05). These subjects also have significantly lower PRA (F = 4.2, P= 0.017). Albeit uncommon, 40% of homozygotes of the alpha-adducin polymorphism had LVH (odds ratio, 15.1; 95% confidence interval, 3.0-82.1). CONCLUSIONS: The homozygotic state of the allele of alpha-adducin polymorphism is independently associated with increased LV mass and low PRA. These data suggest that genetic considerations may contribute importantly to risk stratification, and perhaps therapeutic interventions targeted at LVH and the renin-angiotensin system in hypertensive patients.

Adult↗

PubMed2005

CYP11B2 gene polymorphisms and hypertension in highlanders accustomed to high salt intake.

BACKGROUND: High salt intake is the main determinant of hypertension. The alleles, which once had adaptive value in the salt-poor environment, by promoting salt retention, now induce hypertension. It would be interesting to determine whether the variant alleles of the aldosterone synthase gene (CYP11B2), if related to exaggerated expression/altered activity, are associated with hypertension when combined with a salt-rich diet. OBJECTIVE: To investigate the -344T/C, K173R and intron-2 conversion polymorphisms of CYP11B2 for an association with hypertension in highlanders accustomed to a high salt intake. DESIGN AND METHODS: Three CYP11B2 polymorphisms were compared with respect to frequencies and clinical characteristics in 190 normotensive highlanders (NHLs) and 100 hypertensive highlanders (HHLs). One-way ANOVA, chi2 test and logistic regression analysis were carried out to investigate the association of these polymorphisms with hypertension. RESULTS: The HHLs had significantly higher systolic blood pressure (SBP), diastolic blood pressure (DBP) (P < 0.0001), body mass index (BMI) (P = 0.0002), plasma aldosterone levels (P = 0.03) and aldosterone to plasma renin ratio (ARR) (P < 0.0001) and lower plasma renin activity (PRA) (P = 0.007). The -344T/C and K173R polymorphisms were in complete linkage disequilibrium with each other and the intron-2 conversion allele was in absolute association with the T allele. The TC/CC genotypes correlated with higher BMI when compared with TT genotype in the NHLs and the HHLs (P = 0.002 and 0.004, respectively). The intron-2 conversion heterozygotes/homozygotes correlated with higher SBP in the HHLs (P = 0.03) and significantly higher ARR when compared to IwIw (P = 0.02). Genotype combinations between the -344T/C and intron-2 conversion polymorphisms revealed that combinations with TC or CC genotypes inclined towards higher BMI in both the groups (P < 0.05). CONCLUSIONS: Our findings showed a correlation of C allele with high BMI, suggesting that -344T/C polymorphism is in linkage disequilibrium with a functional polymorphism on the adjacent 11-beta hydroxylase gene. The correlation of the intron-2 conversion allele with high SBP and ARR associates it with hypertension. The intron-2 conversion could be a functional variant, since it has been suggested to lead to overexpression of the gene; however, the presence of another functional variant in linkage disequilibrium within the gene cannot be ruled out.

Adult↗

PubMed2004

Association of paraoxonase 1 polymorphism with beta-cell function: a case of molecular heterosis.

Paraoxonase 1 (PON1) is an antioxidant enzyme that inhibits the oxidative modification of LDL. Since PON1 has been shown to express in pancreatic islets and oxidative stress plays a role in beta-cell dysfunction, we investigated the impact of the PON1 polymorphisms on beta-cell function. This study included 84 healthy and glucose-tolerant white subjects who underwent an oral glucose tolerance test. Beta-cell function (1stPHS and 2ndPHS) was estimated according to the formulae published by Stumvoll et al. The relationship of the L55M and Q192R polymorphisms to beta-cell function was examined. Allelic frequency in this population was 0.37 for the M allele and 0.30 for the R allele. For the L55M polymorphism, the LM genotype had the lowest 1stPHS (P = 0.009) and 2ndPHS (P = 0.007), indicating molecular heterosis. Multivariate analyses confirmed that the L55M polymorphism was an independent determinant for 1stPHS (P = 0.016) and 2ndPHS (P = 0.009), after adjustment for covariates. For the Q192M polymorphism, no difference was noted in 1stPHS and 2ndPHS. We observed the L55M polymorphism of the PON1 gene as an independent determinant for beta-cell function in glucose-tolerant whites. Our observations suggest that this polymorphism could play a role in beta-cell dysfunction.

Adult↗

PubMed2003

Case-control and linkage disequilibrium studies of the tryptophan hydroxylase gene polymorphisms and major depressive disorder.

OBJECTIVES: Alterations in the level of the serotonin, serotonin uptake and the number of binding sites have been linked to affective illness. We investigated the association of tryptophan hydroxylase gene polymorphisms and unipolar depression in a case-control study design. METHODS: Patients and ethnically matched controls were genotyped for three polymorphisms of the tryptophan hydroxylase gene. RESULTS Significant difference in genotype frequency between patient and control groups was observed for the IVS7+218A >C polymorphism but not for the two promoter polymorphisms -1067G >A and -347T >G. Strong linkage disequilibrium among the three polymorphisms was also observed. CONCLUSIONS: As the sample size was small, the positive association would need to be replicated by family-based association studies or in a larger set of samples. As our results did not indicate association with either of the two promoter polymorphisms, there is a need to continue the search for the causative variant directly involved in the susceptibility to unipolar depression in Chinese as this polymorphism within the intron might not be the true susceptibility variant.

Case-Control Studies↗

PubMedDate not supplied

Association of estrogen and vitamin D receptor gene polymorphisms with tooth loss and oral bone loss in Japanese postmenopausal women.

OBJECTIVE: To investigate the relationship between estrogen receptor (ER) and vitamin D receptor (VDR) gene polymorphisms and tooth loss, oral bone loss, and postcranial bone mineral density (BMD) in Japanese postmenopausal women. DESIGN: Polymorphisms at the ER PvuII and XbaI and VDR BsmI gene sites, number of teeth remaining, oral bone mass, and BMD of the lumbar spine and the hip were evaluated in 149 Japanese postmenopausal women. RESULTS: The distribution of ER PvuII and XbaI and VDR BsmI restriction fragment length polymorphisms was as follows: pp, 30.2%; Pp, 49.7%; PP, 20.1%; xx, 71.8%; Xx, 22.5%; XX, 2.7%; bb, 76.5%; Bb, 22.2%; and BB, 1.3%. Analysis of covariance adjusted for confounding variables revealed that participants with pp allele had fewer teeth remaining than did those with P allele. There were no significant differences in oral bone mass and postcranial BMD among three alleles at the PvuII site. Participants with X and bb allele had less oral bone mass and lower postcranial BMD than did those with xx and B allele, respectively. We could not clarify the positive associations between XbaI and BsmI polymorphism and number of teeth. CONCLUSIONS: PvuII polymorphism was associated with tooth loss, but not with oral bone mass and postcranial BMD. XbaI and BsmI polymorphisms may be associated with bone mass or density; however, PvuII polymorphism might contribute to another unknown pathway related to tooth loss.

Adult↗

PubMed2005

Polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of infection in critically ill adults.

OBJECTIVE: To test for the association of single nucleotide polymorphisms of the innate immunity receptors cluster of differentiation (CD)-14, mannose-binding lectin, and Toll-like receptor-2 with clinical phenotype in critically ill patients with systemic inflammatory response syndrome. DESIGN: Genetic association study. SETTING: Tertiary care mixed medical-surgery intensive care unit at St. Paul's Hospital, Vancouver, BC, a teaching hospital associated with the University of British Columbia. PATIENTS: A cohort of 252 critically ill Caucasians with systemic inflammatory response syndrome. INTERVENTIONS: DNA was extracted from discarded blood. Clinical data were gathered by retrospective chart review. MEASUREMENTS AND MAIN RESULTS: C-159T CD14, the X/Y and B, C, and D polymorphisms of mannose-binding lectin, and T-16933A Toll-like receptor-2 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. We tested for association of genotype with prevalence of positive bacterial cultures, type of organism (Gram-positive, Gram-negative, other), sepsis and septic shock at admission to the intensive care unit, and 28-day survival. CD14 -159TT was associated with increased prevalence of positive bacterial cultures and with Gram-negative bacteria. Mannose-binding lectin haplotype pairs XO/O and O/O were also associated with increased prevalence of positive bacterial cultures but not with a specific organism class. Toll-like receptor-2 -16933AA was associated with increased prevalence of sepsis and with Gram-positive bacteria. In contrast, the polymorphisms were not associated with increased prevalence of septic shock or altered 28-day survival. CONCLUSIONS: Single nucleotide polymorphisms in CD14, mannose-binding lectin, and Toll-like receptor-2 are associated with increased prevalence of positive bacterial cultures and sepsis but not with altered prevalence of septic shock or decreased 28-day survival. Furthermore, CD14 single nucleotide polymorphisms were associated with Gram-negative bacteria and Toll-like receptor-2 with Gram-positive bacteria, whereas mannose-binding lectin was not associated with a particular organism class. Thus, single nucleotide polymorphisms in innate immunity receptors may alter recognition and clearance of bacteria without changing outcomes of critically ill adults with systemic inflammatory response syndrome.

Adult↗

PubMed2006

Association of V227A PPARalpha polymorphism with altered serum biochemistry and alcohol drinking in Japanese men.

OBJECTIVES: Peroxisome proliferator-activated receptor (PPAR) alpha plays a major role in alcoholic liver disease in rodents. The two-fold objective of our study was to determine the presence of PPARalpha polymorphisms and their frequencies in Japanese populations and then to evaluate the effects of any alleles on metabolic parameters and alcohol drinking. METHODS: Analysis of coding SNP in PPARalpha was performed in 706 Japanese men; from these subjects 655 men were further studied after exclusion criteria were applied. RESULTS: PPARalpha-V227A, which has not been reported in Europe and North America as a major polymorphism, was discovered with the frequency of 0.05. PPARalpha-L162V was found in European and North American populations, but not in Japanese, thus confirming the ethnic differences in PPARalpha allele frequencies. The A227 allele was associated with increased serum concentrations of gamma glutamyltranspeptidase. In non-drinkers, the total cholesterol (TC) levels were significantly lower in those having the PPARalpha-V227A polymorphism. In drinkers, however, it was comparable among V227A polymorphisms, and conversely higher in those having both A227 and aldehyde dehydrogenase 2 (ALDH2) variants when further divided according to the ALDH2 polymorphism. Significant interactions between PPARalpha-V227A polymorphism and drinking were also found for TC, triglyceride levels and AST/ALT ratios. These results suggest that the activity of the A227 allele without drinking may be higher than in wild-type allele, but its activity may become lower during drinking habits. CONCLUSION: PPARalpha-V227A is a major polymorphism in the Japanese population, and its activity may be greater compared to wild-type, but decreased by alcohol drinking.

Alcohol Drinking↗

PubMed2006

Cholesterol and saturated fat intake determine the effect of polymorphisms at ABCG5/ABCG8 genes on lipid levels in children.

PURPOSE: Analysis of mutations in genes of the cholesterol metabolic pathway has not completely explained the interindividual variability of blood cholesterol concentrations attributed to gene-nutrient interactions. Thus, we analyzed polymorphisms in the ABCG5 and ABCG8 genes, involved in the regulation of intestinal cholesterol absorption, with special interest in a potential interaction with diet to determine lipid levels. METHODS: The polymorphisms ABCG5 C1950G (Gln604Glu) and ABCG8 C1895T (Ala640Val) were determined by polymerase chain reaction and restriction analysis in 1227 healthy school children, aged 6 to 8 years. RESULTS: No significant differences were found in blood lipid levels between subjects with different genotypes of the two analyzed polymorphisms. However, important differences appeared when separating subjects by their different lipid intake. The presence of the ABCG8 C1895T and ABCG5 C1950G polymorphisms was associated with different plasma total cholesterol, low-density lipoprotein cholesterol complex, and apolipoprotein B levels only in low-cholesterol consumers (significantly for the C1895T polymorphism), and among children within the lower tertile of saturated fat intake (significantly for the C1950G polymorphism). CONCLUSION: Polymorphisms at the half-transporter ABCG5 and ABCG8 genes affect blood cholesterol concentrations in prepubertal children by influencing dietary responsiveness. This highly significant gene-nutrient interaction could explain the great individual differences in the plasma lipid response to cholesterol and fat intake.

ATP Binding Cassette Transporter, Subfamily G, Mem↗