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 1,171 records · Page 65Linked to original sources

PubMed2002

[Crystalline polymorphism of eflucimibe].

The importance, in therapeutics, of the concept of bioavailability and on-going quality research in the formulation of a drug has prompted us to examine the crystalline polymorphism of eflucimibe as from the research phase. This study has been carried out by re-crystallization of the product in organic solvents having a different polarity in a variety of experimental temperature and pressure conditions, then, subsequently, by re-cooling the previously dissolved substance. The analytical methods applied to identify and then describe the polymorphic forms are thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction from synchrotron radiation (XRPD), infrared spectrometry (IR), solid-state nuclear magnetic resonance spectrometry (SSNMR) and lastly maximum solubility measurements. By means of XRPD, two polymorphic forms called A and B have been clearly identified at ambient temperature. These two crystalline forms were obtained in a reproducible way, then described by DSC, XRPD, IR and SSNMR. Differential scanning calorimetry analysis has shown for polymorphic form A two endothermic phenomena with low energy at about 35 masculine and 118 degrees C attributed by XRDP to conformational polymorphism. The complex endothermic event that extends between 75 masculine and 105 degrees C appears to correspond to successive alterations of a lamellar structure. The solid-solid transition observed at 110 degrees C is due to a change of crystalline phase, then the melting point occurring at about 130 degrees C. For form B, two changes of crystalline phase are clearly observed at about 80 masculine and 120 degrees C. The reversibility of these changes was observed by thermomicroscopy in polarized light. Form A, which is less soluble in absolute ethanol than form B, is the more stable thermodynamically in the temperature range from 25 masculine to 50 degrees C where the data have been obtained. The Van't Hoff diagram layout for each polymorphic form appears to reveal an A<-->B transition temperature in a temperature range lower than 25 degrees C. This study, undertaken as from the research phase, has enabled us to highlight the polymorphism of this new chemical entity by means of XRDP by explaining the nature of the endothermic phenomena observed by DSC, and lastly identify the thermodynamically more stable polymorphic form, thus contributing to a better knowledge of this future drug.

Anilides↗

PubMed2005

[Variable number of tandem repeats polymorphism of MUC20 is associated with the progression of IgA nephropathy].

OBJECTIVE: The MUC20 gene is a novel up-regulated gene that was identified in renal tissues of patients with IgA nephropathy (IgAN) by restriction endonucleolytic analysis of differentially expressed sequences. The variable number of tandem repeats (VNTR) polymorphism of MUC20 was detected in different cell lines. In this study we determined the distribution of MUC20 VNTR polymorphism in the healthy population, and the association between the MUC20 VNTR polymorphism and the pathogenesis or progression of IgAN. METHODS: 282 healthy and 503 proved IgAN patients by biopsy were involved in this investigation. 113 patients had been followed-up for 3.5 +/- 1.5 years. Genomic DNAs were extracted from peripheral blood leucocytes. MUC20 VNTR polymorphism was detected by PCR amplification and several representational PCR products were confirmed by sequencing. The MUC20 genes were divided into small alleles (repeat times 3) according to the repeat times of MUC20 VNTR. These patients were classified into group SS, SL and LL. MUC20 allele frequencies and genotypes of IgAN patients were analyzed and compared with healthy population. In addition, the associations of MUC20 polymorphism with the clinical and pathological parameters at the time of renal biopsy were analyzed. The data followed up in different groups were compared. RESULTS: There was MUC20 VNTR polymorphism in healthy population with 2 - 6 repeats. The repeat fragment was 57bp. The most frequent alleles included 3(R(3)) and 4(R(4)) repeats; otherwise the least ones included 6(R(6)) repeats. The most frequent genotype was R(3)R(4), then R(3)R(3) and R(4)R(4); the least ones were R(2)R(2), R(3)R(6) and R(5)R(5). The frequencies of MUC20 alleles and genotypes in the IgAN patients were similar to healthy population. Initial ages, blood pressure, proteinuria, and renal function did not differ significantly among the three groups. There was no difference of the urinary osmotic pressure, urinary NAG (N-acetyl-B-D-glucosaminidase) and alpha1 microglobulin (alpha1-MG), and the semiquantitative scores of renal interstitial fibrosis and tubular atrophy in the three groups. IgAN patients with SL/LL genotype had higher odds ratio for progression of renal function (OR = 7.29, 95% CI: 1.68 - 31.60, P = 0.008) than the SS genotype. CONCLUSIONS: There were MUC20 VNTR polymorphisms in the healthy population. The polymorphism did not associate with the pathogenesis and the clinico-pathological parameters at the time of renal biopsy. The SL/LL genotype was likely to be a risk factor for rapid progression of renal function in the patients with IgAN.

Adolescent↗

PubMed2003

Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity.

OBJECTIVE: To determine whether functional cytokine gene polymorphisms influence disease susceptibility and phenotype in patients with psoriatic arthritis (PsA). METHODS: DNA was obtained from 147 PsA patients and 389 controls. Seven functional proinflammatory (interleukin-1beta [IL-1beta] +3953, IL-6 -174, tumor necrosis factor alpha [TNFalpha] -308, TNFbeta +252) and antiinflammatory (IL-10 -1082, IL-10 -592, IL-1 receptor antagonist [intron 2, 86 bp, variable-number tandem repeat]) gene polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism assays. RESULTS: No significant difference in genotype frequencies was observed between the control and the PsA patient populations, and no association with Steinbrocker functional class, disease classification (polyarticular or oligoarticular), presence of spinal involvement, or age at PsA onset was observed. The presence of joint erosions was significantly associated with the TNFalpha -308 and TNFbeta +252 polymorphisms (P < 0.0001 and P = 0.0017, respectively). Frequencies of the TNFalpha -308 and TNFbeta +252 genotypes were also significantly different (P = 0.0078 and P = 0.0486, respectively) in a group of progressors (patients with early PsA in whom the number of joint erosions in the hands and feet increased over a median interval of 24 months) compared with a group of nonprogressors. Age at psoriasis onset was significantly associated with the TNFbeta +252 and TNFalpha -308 polymorphisms (P = 0.0003 and P = 0.0081, respectively). The TNFB2B2 and TNFalpha -308 AA genotypes were associated with the earliest mean ages at psoriasis onset. CONCLUSION: The TNFalpha -308 and TNFbeta +252 polymorphisms were significantly associated with age at psoriasis onset, presence of joint erosions in PsA, and progression of joint erosions in early PsA. TNF gene polymorphisms may be useful prognostic markers in PsA, and these results support the rationale for using anti-TNF treatment in patients with severe, progressive PsA.

Adolescent↗

PubMed2003

Detection of UGT1A10 polymorphisms and their association with orolaryngeal carcinoma risk.

BACKGROUND: UGT1A10 exhibits glucuronidating activity against metabolites of the tobacco smoke carcinogen, benzo(a)pyrene, and is expressed highly in numerous target tissues for tobacco-related cancers including the upper aerodigestive tract. The current study was conducted to determine the prevalence of genetic polymorphisms in the UGT1A10-specific region of the UDP-glucuronosyltransferase family 1A locus and their relationship with risk for orolaryngeal carcinoma. METHODS: The authors analyzed UGT1A10-specific sequences in a population of black, white, and Asian individuals. Ten UGT1A10 alleles were identified by direct sequencing of UGT1A10 sequences amplified by polymerase chain reaction (PCR) using DNA purified from buccal cell swabs that were taken from individual subjects. RESULTS: In addition to three silent polymorphisms, three missense polymorphisms were found at codons 139 (Glu > Lys), 240 (Thr > Met), and 244 (Leu > Ile). Using PCR-restriction fragment length polymorphism analysis of buccal cell DNA, the prevalence of the UGT1A10(240Met) variant was less than 0.01% in whites and blacks. Similarly, the prevalence of both the UGT1A10(139Lys) and UGT1A10(244Ile) variants was less than 0.01% in whites but it was significantly higher (0.04 and 0.05, respectively, P < 0.01) in blacks. None of the missense UGT1A10 variants were found in any of the Asian individuals examined. In a case-control study of black individuals, a significant association with orolaryngeal carcinoma risk was found in persons with at least 1 UGT1A10(139Lys) allele (crude odds ratio, 0.29 [95% confidence interval, 0.10-0.81]; adjusted odds ratio, 0.20 [95% confidence interval, 0.05-0.87]). No association was observed for the codon 244 (Leu > Ile) polymorphism. CONCLUSIONS: The data from the current study show that the UGT1A10 gene has several low-frequency missense polymorphisms and that the codon 139 polymorphism is an independent risk factor for orolaryngeal carcinoma in blacks.

Alcohol Drinking↗

PubMedDate not supplied

The use of denaturing gradient gel electrophoresis to screen for DNA sequence polymorphisms in the human factor VIII gene.

We describe the use of denaturing gradient gel electrophoresis to screen for DNA sequence polymorphisms in the human factor VIII gene. DNA fragments that differ in sequence by only a single base pair can be separated on denaturing gradient gels due to changes in their melting behavior. Previous studies have demonstrated the use of denaturing gradient gels to detect sequence changes in human genomic DNA, including mutations in the beta globin gene and polymorphisms on chromosome 20. We have begun to use denaturing gradient gels to look for polymorphisms within the human factor VIII gene. The DNA sequences of seven cloned fragments from introns in the human factor VIII gene were determined and used to predict a melting map for each fragment. The melting behavior of each cloned fragment was evaluated by electrophoresis into denaturing gradient gels. Appropriate fragments were then used as radioactive probes for hybridization to human DNA samples that had been digested with restriction enzymes. Heteroduplexes formed between the probe and genomic DNA samples were electrophoresed into denaturing gradient gels. The final positions of heteroduplex bands were determined by autoradiography. We describe a general approach for using denaturing gradient gel electrophoresis to find DNA polymorphisms, with particular emphasis on the predictive value of DNA sequence data. We compare the efficiency of polymorphism detection by denaturing gradient gel electrophoresis with detection by restriction fragment length polymorphism (RFLP) analysis. The factor VIII gene appears to have a low level of DNA sequence polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed2004

Heterozygote deficiency in thymidylate synthase enhancer region polymorphism genotype distribution in Hungarian colorectal cancer patients.

Thymidylate synthase (TS) gene polymorphisms are important as prognostic factors in cancer chemotherapy, but recent results describe that the TS enhancer region (TSER) polymorphic genotypes may also modulate risk for malignancies. Two functionally important and ethnically diverse polymorphisms are present on the TS transcript, TSER, a repeat polymorphism (2 or 3 repeats; 2R, 3R) affecting TS expression, and a 6 bp ins/del polymorphism on the 3' UTR (position TS1494, del6 or ins6), which may influence mRNA stability. Hungarian population has one of the highest colorectal cancer (CRC) mortality rates in Europe, and several elevated dietary risk factors affect a large part of the population. In our study (99 primary CRC cases), population analysis of the patient group genotype frequencies revealed a departure from the Hardy-Weinberg equilibrium and significant heterozygote deficiency (p < 0.05) at the TSER locus. Despite the strong linkage between the 2 polymorphic loci, case TS1494del genotype frequencies were normally distributed, as well as the genotype frequencies of the healthy control population (n = 102), at both loci. Case-control comparison demonstrated a lower relative risk of TSER heterozygotes (OR = 0.47; CI = 0.27-0.83; p = 0.008) and a possible higher prevalence of the 3R3R&ins6/del6 in the CRC group. The observation that heterozygotes are those less susceptible for CRC in the Hungarian population may support the possibility of 2 different pathways in which TS may play a role in colorectal carcinogenesis, probably nutrient (or folate)-dependently. The lack of similar genotype effect seen with TS1494del polymorphism and the increased presence of one genotype combination (3R3R&ins6/del6) in the patient group suggest a possible TS haplotype effect influencing CRC risk.

3' Untranslated Regions↗

PubMed1993

Polymorphisms in the apolipoprotein B-100 gene contributes to normal variation in plasma lipids in 464 Danish men born in 1948.

We have studied the possible association of 5 polymorphisms in the apoB gene [a 9-bp insertion/deletion length polymorphism in the signal peptide coding region, XbaI, MspI, and EcoRI restriction fragment length polymorphisms (RFLPs) and a 15-bp variable number of tandem repeats (VNTR) region 3' to the apoB gene] with plasma concentrations of cholesterol, high density lipoprotein cholesterol, triglycerides and apolipoprotein B-100 in 464 randomly selected Danish men born in 1948. The XbaI RFLP and the insertion/deletion length polymorphism were significantly associated with plasma concentration and inter-individual variation of cholesterol and apolipoprotein B-100 (1.77% and 1.37% of sample variance in cholesterol, and 1.4% and 1.39% of sample variance in apoB). The association was particularly strong in men with a body mass index less than 25 kg/m2 (the mean value of the whole cohort) (3.43% and 2.93% of sample variance in cholesterol, and 3.1% and 2.13% of sample variance in apoB). The XbaI RFLP and the insertion/deletion length polymorphism were in strong linkage disequilibrium, explaining why independent associations of these two polymorphisms with cholesterol and apoB could not be established. There were no other associations between apoB gene polymorphisms and lipoprotein components.

Alleles↗

PubMed1988

Limited polymorphism of both classes of MHC genes in four different species of the Balkan mole rat.

We analyzed the restriction fragment length polymorphism of class I and class II MHC genes in DNA from 20 individuals belonging to the four different species of the complex of species of Balkan mole rats Spalax leucodon captured at four different localities in Yugoslavia. All populations were tested with four restriction enzymes and one conserved mouse probe for each of the two classes of MHC genes. The probes employed detect either limited polymorphism of class I genes or lack of polymorphic bands containing class II genes. Of the two other subterranean rodents that have been studied, four karyotype forms of the Israeli mole rat show polymorphism in both classes of MHC genes similar to the one found in all other mammals (Nizetić et al. 1985), and the Syrian hamster shows limited polymorphism of class I genes and high polymorphism of class II genes (McGuire et al. 1985). Balkan mole rats belong to a new group in this respect, different from all mammals studied so far, since they apparently show limited polymorphism of both classes of MHC genes.

Animals↗

PubMed1989

The T-cell receptor alpha, beta and gamma polymorphism in Japanese.

Polymorphism in the genes encoding the alpha (alpha), beta (beta) and gamma (gamma) chains of the human T-cell receptors was analyzed both in population and family studies. Against twelve unrelated Japanese, several out of the 15 restriction endonucleases tested, revealed restriction fragment length polymorphism. The segregation of the polymorphic fragments were confirmed among 15 members of three families. In most of the cases paternal and/or maternal haplotypes could be assigned. By testing the polymorphic enzymes among the random healthy Japanese, the frequency of each polymorphic fragment was then determined. Although the polymorphism found in this study was similar to that reported in Caucasians, some differences were observed. Such differences are discussed. The restriction fragment length polymorphism in both population and family studies, derived from alpha, beta and gamma chains of the T-cell receptor found in this report, might be useful markers for genetic analysis of the T-cell function in relation to immunological disorders.

Humans↗

PubMed2000

Polymorphisms in the genes encoding platelet-derived growth factor A and alpha receptor.

Platelet-derived growth factors (PDGFs) may play an important role in the development of atherosclerosis acting as chemoattractants and mitogens for vascular smooth muscle cells and macrophages. Three dimeric forms of PDGF (AA, AB, BB) have different activities due to distinct binding properties mediated by two types of PDGF receptors (Ralpha, Rbeta). To investigate the possible contribution of molecular variants in the human PDGF-A and PDGF-Ralpha genes to coronary heart disease we screened these genes for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism analysis. A total of 600 men with myocardial infarction and 717 age-matched male controls from four populations in Northern Ireland and France (the ECTIM Study) were gneotyped for newly identified polymorphisms in the genes encoding PDGF-A (C-26IN3T, H69H, C+12IN5T) and PDGF-Ralpha [-1630 I/D (+/-AACTT), A-1506G, C-1390G, G-956A, C-908A, G-793T, +69 I/D (+/-GA)] using allele-specific oligonucleotides. All PDGF-Ralpha polymorphisms, except C-908A, involving a nucleotide change in a common consensus site for GCF and SP-1 transcription factors, were in nearly complete association, generating two major haplotypes. The PDGF-A and PDGF-Ralpha polymorphisms provided a heterozygosity of 0.69 and 0.40, respectively. Genotype and allele frequencies of the PDGF-A and PDGF-Ralpha polymorphisms did not differ between patients with myocardial infarction and controls in either country. None of the polymorphisms investigated was associated with blood pressure, coronary artery stenosis, or any biochemical parameter available in the ECTIM Study.

Adult↗

PubMed1999

The vitamin D receptor start codon polymorphism (Fok1) and bone mineral density in premenopausal women in Taiwan.

The vitamin D receptor gene (VDRG) polymorphism as a factor of bone turnover rate or bone mineral density (BMD) is a controversial issue, especially in different ethnic populations. In addition to intron 8 (Bsm1, Taq1) and exon 9 (Apa1), VDRG polymorphism is present at its translation initiation site on exon 2. The VDRG has two translation initiation sites. The first shows a thymine/cytosine polymorphism and can be detected by restriction fragment length polymorphism (RFLP) using the endonuclease Fok1. This start codon polymorphism (SCP) of the VDRG was detected by polymerase chain reaction and then by RFLP with Fok1. While the f allele was assigned for the presence of the restriction site, the F allele was assigned for the absence of the restriction site, and the encoded vitamin D receptor is shorter by three amino acids. We examined the association between this SCP of the VDRG and bone turnover as well as BMD in 101 premenopausal Taiwanese women aged 40-53 years. Total body bone mineral content and BMD of proximal femur and lumbar spine were measured by dual-energy X-ray absorptiometry. We found a prevalence of 39.6% for the f allele of the VDRG. The frequencies of FF, Ff and ff genotypes were 35.6%, 49.5% and 14.9%, respectively. There was no statistically significant difference in BMD at any site or bone turnover markers among the three Fok1 genotypes (FF, Ff and ff). The SCP is independent of Bsm1, Apa1 or Taq1 polymorphisms of the VDRG at intron 8 and exon 9. In conclusion, the SCP polymorphism detected by endonuclease Fok1 does not significantly influence BMD or bone turnover in premenopausal women in Taiwan.

Absorptiometry, Photon↗

PubMed2002

Investigation of the genetic influence of the OPG, VDR (Fok1), and COLIA1 Sp1 polymorphisms on BMD in the Irish population.

Low bone mineral density (BMD) is a major risk factor for the development of osteoporosis and there is strong evidence to suggest that the procurement and preservation of peak BMD is genetically determined. In an effort to identify factors responsible for susceptibility to low BMD in the Irish population, we investigated its possible association with polymorphisms in the Osteoprotegerin (OPG) gene, Type I collagen alpha 1 (COLIA1) Sp1 binding site and vitamin D receptor (VDR) start codon. Following a systematic screening of the regulatory and coding regions of the OPG gene, we identified a novel G1181C polymorphism in exon 1 and a T950C polymorphism in the promoter region of the OPG gene. Participants were recruited from the Bone Densitometry Unit of Cork University Hospital, including 381 postmenopausal women aged 61.26 +/- 8.50 (mean +/- SD) and 130 premenopausal women aged 46.30 +/- 6.50 (mean +/- SD). Following association analysis using both the premenopausal and postmenopausal cohorts we found that postmenopausal women carrying one or more C alleles of the G1181C polymorphism had 14.8% lower BMD (P = 0.05) at the lumbar spine and 14.4% lower BMD (P = 0.04) at the FN. However, both were nonsignificant when the Bonferroni correction factor (0.01 significance level) was applied to correct for multiple hypothesis testing. We found no association between alleles of the T950C OPG polymorphism and BMD. Similarly, we have found a lack of association between the VDR (fok1) polymorphism or COLIA1 Sp1 polymorphism and low BMD in either postmenopausal or premenopausal women in this population.

Base Sequence↗

PubMed2004

The -1997 G/T polymorphism in the COLIA1 upstream regulatory region is associated with hip bone mineral density (BMD) in Chinese nuclear families.

Type I collagen is the most abundant protein of bone matrix, and the collagen type I alpha 1(COLIA1) gene has been considered one of the most important candidate genes for osteoporosis. In this study, we simultaneously tested linkage and/or association of the -1997 G/T polymorphism in the COLIA1 upstream regulatory region with the variation of bone mineral density (BMD) in 1263 subjects from 402 Chinese nuclear families, consisted of both parents and at least one healthy female offspring from 20 to 45 years of age. All the subjects were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). BMD of the lumbar spine (L1-L4) and hip (respective and combined phenotype of the femoral neck, trochanter, and intertrochanter) was measured by dual-energy X-ray absorptiometry (DXA). By using the tests implemented in program QTDT (quantitative transmission disequilibrium test), we found significant within-family association (via TDT) between the -1997 G/T polymorphism with BMD variation at all the hip sites (respective and combined phenotypes, P < 0.05). The amount of BMD variation explained by the -1997G/T polymorphism was 1.6%, 2.0%, 1.2%, and 1.3% at the total hip, femoral neck, trochanter, and intertrochanter, respectively. Because of the limited number of sib pairs in this sample, we did not find evidence of linkage. In summary, the -1997 G/T polymorphism in the COLIA1 gene is likely to be in linkage disequilibrium with a nearby functional polymorphism affecting hip BMD, or the -1997 G/T polymorphism itself may have an important effect on the variation of hip BMD in our Chinese sample.

Adult↗

PubMed1996

Identification of the nucleotide substitution that generates the fourth polymorphic site in human deoxyribonuclease I (DNase I).

In addition to the three polymorphic sites responsible for protein polymorphism, a new polymorphic site has been identified in intron 7 of the human deoxyribonuclease I (DNase I) gene. Three phenotypes were observed on single-strand conformational polymorphism analysis of a 266-bp polymerase chain reaction-amplified fragment containing exon 7 and part of intron 7 of the human DNase I gene. DNA sequencing analysis demonstrated that a C-G substitution occurred at position 1978 in intron 7. This substitution was confirmed by restriction fragment length polymorphism analysis, since a new Msp1 site is created by the substitution. Population and family studies showed that the inheritance of the genotypes for DNase I C1978G polymorphism is controlled by two codominant alleles, tentatively designated DNASE1*1978C and *1978G. The gene frequencies in a Japanese population were significantly different from those in a Caucasian (German) population. The C1978G polymorphism is in linkage disequilibrium with the common DNase I protein phenotypes 1, 1-2, and 2.

Base Sequence↗

PubMed2001

Combined segregation-linkage analysis of plasma thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels with TAFI gene polymorphisms.

By decreasing plasminogen binding to fibrin surface, the thrombin activatable fibrinolysis inhibitor (TAFI) has been hypothesized to constitute an early marker for atherothrombotic diseases. Previous studies have shown that plasma TAFI levels exhibit a high interindividual variability that is only poorly explained by lifestyle factors. Several polymorphisms of the TAFI gene have been described, and a combination of a C+1542G substitution in the 3' untranslated region and an Ala147Thr amino acid change has been shown to explain 60% of TAFI variability in a sample of unrelated individuals. A segregation-linkage analysis was performed to determine whether these polymorphisms are directly involved in the genetic regulation of TAFI levels, or whether they are only markers in linkage disequilibrium (LD) with unmeasured TAFI-linked quantitative trait loci (QTLs). The sample consisted of 97 healthy nuclear families from the Stanislas Cohort. The C+1542G and Ala147Thr polymorphisms were in complete negative LD, with minor allele frequencies of 0.27 and 0.28, respectively. Results of the segregation-linkage analysis provided evidence of two TAFI-linked QTLs in LD with the two measured polymorphisms, which would explain 78% of the TAFI variance, as compared with 55% explained by the C+1542G and the Ala147Thr polymorphisms combined. The two putative QTLs would have minor allele frequencies of 0.45 and 0.32, respectively. The hypothesis that one of the measured polymorphisms is one of the QTLs was rejected. The putative QTLs also did not seem compatible with the other TAFI gene polymorphisms that we have previously described. More extensive sequencing of the TAFI gene is necessary to identify the functional variants.

Adolescent↗

PubMed2003

A-20C angiotensinogen gene polymorphism and proteinuria in childhood IgA nephropathy.

We have previously reported that the TT genotype of the angiotensinogen gene and the ID/DD genotype of the angiotensin-converting enzyme gene are associated with increased severity of proteinuria in IgA nephropathy in Japanese children. Recently it was reported that polymorphism at -20 from adenine to cytosine in the angiotensinogen gene, increasing the level of this transcript, was associated with the progression of renal dysfunction in adult IgA nephropathy. We therefore investigated whether this polymorphism is involved in IgA nephropathy in Japanese children. We identified this polymorphism in 105 children with IgA nephropathy and 119 healthy adults using polymerase chain reaction/restriction fragment length polymorphism analysis. At the time of biopsy, all patients had normal blood pressure and renal function. There were no differences in the genotypes and allele frequencies of this polymorphism between patients with IgA nephropathy and controls. The number of patients with the AC/CC genotype showing heavy proteinuria (>or=1.0 g/day per m(2) body surface area) at biopsy was significantly higher than that with the AA genotype ( P=0.039, chi-squared test). The AC/CC genotype of this polymorphism may be associated with an increased severity of proteinuria, suggesting that this polymorphism may play a significant role in the progression of IgA nephropathy in Japanese children.

Adenine↗

PubMed2005

A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia.

BACKGROUND: Results of recent DNA microarray analyses of postmortem brains of patients with schizophrenia revealed that expression of the PDZ and LIM domain 5 gene (PDLIM5) is increased. In the present study, we examined whether polymorphisms in PDLIM5 are associated with schizophrenia. METHODS: We screened for mutations in PDLIM5 in 24 Japanese patients with schizophrenia and evaluated the associations of the identified polymorphisms with schizophrenia in a Japanese case-control population (total samples, 278 schizophrenia patients and 462 control subjects). Expression of PDLIM5 was quantified by real-time quantitative polymerase chain reaction (PCR) in postmortem prefrontal cortex of 34 schizophrenia patients. Electrophoretic mobility shift assay (EMSA) was performed to examine whether a polymorphism influences nuclear protein binding. RESULTS: We identified 27 polymorphisms in PDLIM5 and found associations between polymorphisms (rs2433320 and rs2433322) in the 5' region of the gene and schizophrenia (p = .004). Real-time quantitative PCR revealed that these polymorphisms influenced gene expression (p = .007). An EMSA showed that the different alleles of the rs2433320 polymorphism bound differently to nuclear proteins. CONCLUSIONS: These results suggest that PDLIM5 might play a role in genetic susceptibility to schizophrenia.

Adult↗

PubMed2005

Variation in femoral length is associated with polymorphisms in RUNX2 gene.

INTRODUCTION: Bone size is an important determinant of bone strength. Although it is well established that bone size traits are under the strong genetic control, genes involved in their determination are poorly characterized. The major objective of the present study was to test hypothesis of possible association between three RUNX2 SNP polymorphisms (rs2819858, rs1406846, rs2819854) and anthropometrical femoral length (FEML). In addition, the possibility of association between anthropometrical tibial length (TIBL) and stature and chosen RUNX2 polymorphisms was tested. MATERIALS AND METHODS: The study was conducted on 265 nuclear families comprised of a total of 904 individuals. DNA samples were available for 705 individuals, belonging to 212 nuclear families. Three different transmission disequilibrium tests (TDTs), population-based and pedigree-based (PDT) association analyses were implemented in order to test the working hypothesis. RESULTS: The results unambiguously and consistently demonstrated significant association for FEML regardless of the specific polymorphism tested and type of analysis implemented. The P values obtained by TDTs ranged between 0.0155 and 0.0007. The effect of RUNX2 polymorphisms was estimated to explain 1.9% of the total FEML variation after adjustment for sex and age. The data suggested that the strength of association between RUNX2 polymorphisms and FEML may be higher in females (P = 0.007) than in males (P = 0.046), according to PDT. Conversely, no reliable evidence of association between RUNX2 polymorphisms and either TIBL or stature was found. CONCLUSIONS: For the first time, the evidence of association between RUNX2 polymorphisms and FEML was provided. The results of the present research contribute to the deeper understanding of the genetic architecture of femoral size and introduce the issues of site and sex dependency of the extent of RUNX2 effect. Further studies are required to confirm our findings, specifically focused on clinically oriented sites of skeleton, like femoral neck.

Adolescent↗