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Results for “polymorphisms”

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PubMed2005

Analysis of TGF-beta(1) gene polymorphisms in Hong Kong Chinese patients with asthma.

BACKGROUND: The C-509T polymorphism of TGF-beta(1) gene has been associated with asthma and atopy in white populations. OBJECTIVE: We investigated the association between asthma and previously identified polymorphisms at C-509T and T869C of the TGF-beta(1) gene among 250 Chinese patients with asthma and 308 healthy controls in Hong Kong. METHODS: Genotyping was performed on peripheral blood genomic DNA by using PCR-RFLP. RESULTS: There were no differences in the frequencies of genotypes and alleles between patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium (P < .01). Among atopic subjects, significant differences were found in genotype and allele frequencies for T869C polymorphism between patients and controls (P = .014 and P = .019, respectively), and individuals bearing the CC genotype were associated with increased risk for the development of asthma (odds ratio, 2.58; 95% CI, 1.17-5.66; P = .018) after adjusting for age, sex, and smoking status. Individuals with asthma bearing the CT genotype of the C-509T polymorphism had significantly increased risk for severe airflow obstruction compared with individuals who had mild obstruction (odds ratio, 4.00; 95% CI, 1.06-15.08; P = .035). CONCLUSION: Our results indicate that the polymorphisms at C-509T and T869C of the TGF-beta(1) gene are associated with asthma susceptibility in atopic subjects of the Hong Kong Chinese population, and the C-509T polymorphism may play a role in the pathogenesis of airflow obstruction.

Adult↗

PubMed2004

'Interleukin-4 gene polymorphism and its relation to periodontal disease in a Brazilian population of African heritage'.

OBJECTIVES: Host modifying factors, such as genetic predisposition, may increase severity of periodontitis. Genetic polymorphisms in interleukin-4 (IL-4) genes seem to influence host response to microbial challenge. Two IL-4 polymorphisms were found in association with asthma and atopy, and later with aggressive periodontitis in Caucasians. There seems to be a trend for racial differences regarding polymorphisms. Therefore, this study aimed to evaluate if these IL-4 polymorphisms were associated with periodontal disease in a Brazilian population of African heritage. METHODS: Sixty patients were divided into two groups: periodontitis group (n = 30) and control group (n = 30) Blood samples were taken and genomic DNA was amplified by polymerase chain reaction (PCR). Identification of 70 bp repeat polymorphism in intron 2 and in the -590 position of the promoter region was performed through PCR-RFLP and electrophoresis in agarose gel. RESULTS: No significant differences were found in the genotype frequency of the polymorphisms between control and periodontitis group. Chi square test and Mann-Whitney test were used for statistical analysis. CONCLUSIONS: We concluded that the studied IL-4 polymorphisms were not related to periodontal disease susceptibility in this African-American Brazilian population.

Adolescent↗

PubMed2006

Polymorphisms of interleukin-1beta in Japanese patients with hepatitis B virus infection.

BACKGROUND/AIMS: Hepatitis B virus (HBV) induces liver cirrhosis (LC) and hepatocellular carcinoma (HCC) mainly by causing chronic necro-inflammatory hepatic disease. Our aim was to investigate the relationships between the polymorphisms of the interleukin-1B (IL-1B) promoter region and the interleukin-1 receptor antagonist gene (IL-1RN) and disease progression in an HBV-infected Japanese population. METHODS: Genomic DNA was extracted from the peripheral blood of 237 HBV carriers. Polymorphisms in IL-1B and IL-1RN were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR with confronting two-pair primers (PCR-CTPP) methods. These polymorphic sites include the promoter regions of IL-1B at positions -511 and -31, and IL-1RN variable tandem repeats. RESULTS: The IL-1B -31 and -511 loci were in complete linkage disequilibrium, and the frequency of the IL-1B -31 T carrier (IL-1B -31 T/T or T/C) was significantly higher in HBV carriers with LC compared to those without LC (LC; 86.1% vs non-LC; 72.1%, P=0.009). There was no difference in the genotype distribution of the IL-1RN polymorphism. CONCLUSIONS: This is the first report describing the association between IL-1B polymorphism and HBV-related hepatic fibrosis, and our data suggest that IL-1B polymorphisms may be related to disease progression of HBV-related hepatitis in Japan.

Adult↗

PubMed2005

Detection of a single nucleotide polymorphism in the human alpha-lactalbumin gene: implications for human milk proteins.

Variability in the protein composition of breast milk has been observed in many women and is believed to be due to natural variation of the human population. Single nucleotide polymorphisms (SNPs) are present throughout the entire human genome, but the impact of this variation on human milk composition and biological activity and infant nutrition and health is unclear. The goals of this study were to characterize a variant of human alpha-lactalbumin observed in milk from a Filipino population by determining the location of the polymorphism in the amino acid and genomic sequences of alpha-lactalbumin. Milk and blood samples were collected from 20 Filipino women, and milk samples were collected from an additional 450 women from nine different countries. alpha-Lactalbumin concentration was measured by high-performance liquid chromatography (HPLC), and milk samples containing the variant form of the protein were identified with both HPLC and mass spectrometry (MS). The molecular weight of the variant form was measured by MS, and the location of the polymorphism was narrowed down by protein reduction, alkylation and trypsin digestion. Genomic DNA was isolated from whole blood, and the polymorphism location and subject genotype were determined by amplifying the entire coding sequence of human alpha-lactalbumin by PCR, followed by DNA sequencing. A variant form of alpha-lactalbumin was observed in HPLC chromatograms, and the difference in molecular weight was determined by MS (wild type=14,070 Da, variant=14,056 Da). Protein reduction and digestion narrowed the polymorphism between the 33rd and 77th amino acid of the protein. The genetic polymorphism was identified as adenine to guanine, which translates to a substitution from isoleucine to valine at amino acid 46. The frequency of variation was higher in milk from China, Japan and Philippines, which suggests that this polymorphism is most prevalent in Asia. There are SNPs in the genome for human milk proteins and their implications for protein bioactivity and infant nutrition need to be considered.

Amino Acid Sequence↗

PubMed2005

Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients.

The innate recognition of microbial components and subsequent activation of cytokine network are important in the pathophysiology of sepsis. Recently, functional gene polymorphisms in molecules associated with these responses were demonstrated. On the other hand, it has been claimed that there are ethnic differences in genetic polymorphisms. This study investigated toll-like receptor (TLR) 4, CD14, tumor necrosis factor (TNF)-alpha and -beta, and interleukin (IL)-10 gene polymorphisms in 197 Japanese critically ill patients and 214 healthy control subjects to evaluate the influence of these polymorphisms on clinical outcome. No Japanese participant carrying TLR4Asp299Gly or Thr399Ile was detected. No association of CD14-159C/T polymorphisms with genotype frequency or sepsis mortality was observed. Frequency of TNF-alpha-308 GA genotype was significantly higher in the sepsis group than in the control group and TNF-alpha-308GA and IL-10-592CC genotypes were related to poor outcome of sepsis. Ethnic differences in genetic variations are very important issues and the frequencies in this study differ from those previously reported in Caucasians. In conclusion, this study may indicate that TNF-alpha-308G/A and IL-10-592C/A polymorphisms involved in subsequent activation of cytokine network had a larger effect on clinical outcome in patients with sepsis than TLR4Asp299Gly, Thr399Ile, and CD14-159C/T polymorphisms associated with the initial host-microbial interaction.

APACHE↗

PubMed2006

A single nucleotide polymorphism in the plasma PAF acetylhydrolase gene and risk of atherosclerosis in Japanese patients with peripheral artery occlusive disease.

BACKGROUND: Plasma PAF-acetylhydrolase (PAF-AH) gene polymorphisms (G994 --> T in exon 9) and the resulting deficiency of enzyme activity were identified in the Japanese population. The objective of this study was to assess the joint effect of the polymorphism and hypercholesterolemia on risk of atherosclerosis. METHODS AND RESULTS: We performed a case-control study including 150 patients who underwent operation for peripheral arterial occlusive disease (PAOD) and 158 controls matched for age and sex. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF-AH activity was measured in both groups. The patients with multiple atherosclerotic diseases showed higher levels of PAF-AH activities than the patients with only peripheral artery occlusive disease among normal genotypes. PAOD patients were assessed either with or without polymorphism or hypercholesterolemia in regard to accompanying coronary artery disease or stroke. The prevalence of the polymorphism was significantly more frequent in the patients with PAOD. The plasma PAF-AH activity was correlated with total cholesterol and LDL level, and inversely related with HDL in normal genotype (GG) PAOD patients. However, neither the correlation nor the inverse relation was found in patients with the polymorphism. Patients with both hypercholesterolemia and the polymorphisms revealed a relative risk for other atherosclerotic disease of 11.5 (6.0-40.3) compared with normal genotype and normal lipid level. CONCLUSION: The plasma PAF-AH gene polymorphism and hypercholesterolemia may interact and increase the risk of atherosclerosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2006

Polymorphisms in ERCC1 and susceptibility to childhood acute lymphoblastic leukemia in a Chinese population.

Excision repair cross-complementation group 1 (ERCC1) is important in repairing DNA damage and genomic instability, and polymorphisms in ERCC1 may play a role in human tumors. In this study, the relationship of two ERCC1 polymorphisms, 8092C>A and 19007G>A, with susceptibility to acute lymphoblastic leukemia (ALL) was investigated in 183 childhood patients. For the ERCC1 8092C>A polymorphism, individuals carrying the ERCC1 8092CC genotype had a significantly higher risk when compared with those carrying at least one A allele gene (AA/AC). Analysis after stratification for sex showed that the males carrying ERCC1 8092CC genotype were associated with highly significant increased risk of ALL (1.94-fold) but not females. There was no association between ERCC1 19007G>A polymorphism and ALL risk when all patients as a group were analyzed. However, the males carrying ERCC119007A allele were associated with highly significant increased risk of ALL (2.36-fold). For the ERCC1 8092C>A polymorphism, individuals under 8 years old (median age) carrying CC genotype had significantly higher risk. However, the 19007G>A polymorphism was not associated with such age-related ALL risk. These results suggest that the ERCC1 8092C>A polymorphism may be related to the occurrence of childhood ALL in a Chinese population.

Child↗

PubMed2006

The lack of association between monoamine oxidase (MAO) intron 13 polymorphism and platelet MAO-B activity among men.

Monoamine oxidase (MAO), a mitochondrial flavine containing enzyme, exists in two isoenzymes, MAO-A and MAO-B. Platelets contain MAO-B subtype, proposed to be a biomarker for different personality characteristics and vulnerability for substance abuse. The most common polymorphism of MAO-B gene, a single base change (A or G) occurs in intron 13. It has been proposed to be a functional polymorphism, controlling the activity of MAO-B in platelets. The aim of the study was to determine the association between platelet MAO-B activity and MAO-B intron 13 polymorphism in 225 racially and ethnically uniform healthy Caucasian men of the Croatian origin. Our results showed that platelet MAO-B activity did not differ between subjects subdivided into those with < > or < >. This polymorphism of the MAO-B gene did not control the activity of the MAO-B in platelets. Platelet MAO-B activity was associated only with the smoking status, and it was significantly decreased in smokers when compared to nonsmokers. No significant association was found between MAO-B polymorphism and smoking status. In healthy individuals of the Croatian origin, the studied MAO-B polymorphism showed a lack of functional importance in regulating MAO-B activity in platelets. Since different populations may vary in the association between functional polymorphism and the MAO-B activity, and the genotype of transcription factor AP-2 beta was reported to be associated with altered platelet MAO-B activity, and with specific personality traits, further studies on different populations should be conducted to elucidate the molecular mechanism/s regulating platelet MAO-B activity.

Adult↗

PubMed2004

Lack of association between Caucasian lung cancer risk and O6-methylguanine-DNA methyltransferase-codon 178 genetic polymorphism.

The formation of DNA adducts is thought to be a critical step for the induction of chemically induced cancer. O(6)-Methylguanine-DNA methyltransferase (MGMT) is a ubiquitously expressed enzyme that repairs DNA adducts formed by alkylating carcinogens. Thus, genetic polymorphisms of the MGMT that could result in differences in MGMT activity are potential risk factors for cancer. In the present study, we established a convenient and reliable genotyping method for the MGMT codon 178 polymorphism, a Lys (AAG) to Arg (AGG) substitution, using restriction fragment length polymorphism (RFLP), and studied differences in the distribution of this polymorphism in 92 Caucasian lung cancer patients and 85 controls. Frequencies of the "A" and "G" alleles (MGMT codon 178, AAG and AGG, respectively) were 0.91 and 0.09, respectively. The genetic polymorphism of the MGMT codon 178 was linked with that of the MGMT codon 143 (P < 0.05). The distribution of the MGMT codon 178 genetic polymorphism was not significantly different between lung cancer patients and controls. Thus, our study suggests that the MGMT codon 178 (and possibly 143) polymorphisms do not appear to markedly affect lung cancer risk for this population. In addition, we found an apparent 10bp-deletion in the intron before exon 5 by DNA sequencing. Because this "deletion" was observed in all sequenced samples (N = 20), the previously reported human (Caucasian) MGMT gene sequence should be revised to exclude this 10bp segment.

Codon↗

PubMed2005

Correlation of estrogen receptor beta gene polymorphisms with spinal bone mineral density in peri- and post-menopausal Greek women.

Estrogens play a significant role in bone physiology. Their action is mainly exerted through their receptors. Estrogen receptor alpha (ERalpha) plays a major role in bone homeostasis and there is evidence suggesting that estrogen receptor beta (ERbeta) has also an effect on BMD. We investigated the possible effect of two ERbeta gene polymorphisms on spinal bone mineral density (BMD) and metabolic bone markers in Greek women. Spine BMD as well as biochemical bone markers were measured in 147 healthy peri- and post-menopausal women [mean age (S.D.) 54 (7.9) years]. Genotyping was performed for two restriction fragment length polymorphisms (RFLPs) of ERbeta gene, RsaI in exon 5 and AluI in exon 8. For each polymorphism studied the cohort was divided into two groups: the "wild-type" group (RR and AA, respectively) and the "carrier" group including subjects with at least one allele with the restriction site (Rr&rr and Aa&aa, respectively). The distribution of RsaI genotypes was RR: 91.2% (n = 134), Rr: 8.2% (n = 12), and rr: 0.6% (n = 1) and of AluI genotypes AA: 36.7% (n = 54), Aa: 57.2% (n = 84), and aa: 6.1% (n = 9). No linkage disequilibrium was found between the two polymorphic sites studied. Spine BMD did not differ significantly in the two groups of either polymorphism, after adjusting for age, weight, height, and years since menopause [mean BMD (S.D.) for RR 0.841 (0.17) g/cm(2) versus Rr&rr 0.798 (0.13) g/cm(2), p = 0.25, and mean BMD (S.D.) for AA 0.828 (0.16)g/cm(2) versus Aa&aa 0.848 (0.17) g/cm(2), p = 0.32]. No significant differences were noted in metabolic bone markers except for a marginal difference of RR versus Rr/rr in urinary hydroxyproline/creatinine ratio [median (IQR) 3.88 (6.04) micromol/mmol in RR versus 8.2 (4.32) micromol/mmol in Rr/rr, p = 0.05]. Furthermore, no interaction between the two polymorphisms on BMD was found. In conclusion, in a Greek female post-menopausal population, the two ERbeta gene polymorphisms were not associated with BMD, or metabolic bone markers.

Absorptiometry, Photon↗

PubMed2006

A novel approach to characterise pathogen candidate genetic polymorphisms involved in clinical outcome.

Understanding the key factors influencing the clinical outcome of an infection is crucial for early diagnosis and optimised treatment. Despite widespread recognition of the importance of the genetics composition of pathogens, most efforts so far have focused on characterising disease and susceptibility genes in humans. Here, we propose a new flexible and powerful methodological framework to detect candidate genetic polymorphisms influencing clinical outcome from pathogen genomes. The rationale is to use well-supported clades in a phylogeny as statistical predictors for clinical outcomes rather than the individual polymorphisms themselves. This greatly increases the statistical power to detect candidate polymorphisms when analysing a large number of variable sites. In a second step, the candidate polymorphisms are recovered by characterising the polymorphisms that most strongly support the clades predicting the clinical outcome. The modelling approach further allows including host factors and testing for possible interactions between factors. We illustrate the approach by an application on a dataset of hepatitis B polymerase genes. The statistical model retains age at infection as well as six candidate polymorphisms as predictors for clinical outcome (acute, chronic and fulminant). The method is straightforward to apply and computationally effective. While the approach is focused on detecting candidate polymorphisms from pathogen genomes, the method might be more broadly applied for characterising the link between genotype and phenotype while statistically controlling for environmental factors.

Hepatitis B virus↗

PubMed2006

Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study.

Polymorphisms in the APOC3 and APOA5 genes, from the APOA1/APOC3/APOA4/APOA5 gene cluster on chromosome 11q23, have been associated with interindividual variation in plasma triglycerides. APOA5 polymorphisms implicated include 2 in the promoter region (-1131 T/C and -3 A/G) and 1 in exon 2 (+56 C/G). APOC3 polymorphisms implicated include 1 (SstI) in the 3' untranslated region and 1 (-2854 G/T) in the APOC3-APOA4 intergenic region. We analyzed the associations of haplotypes and multilocus genotypes of these polymorphisms on longitudinal serum triglyceride profiles in 360 African American and 823 white subjects from the Bogalusa Heart Study. Subjects were examined from 2 to 8 times (mean +/- SD, 5.4 +/- 1.3) between 1973 and 1996, at ages ranging from 4 to 38 years, with 1978 observations in African Americans and 4465 in whites. Serum triglycerides were significantly higher among whites across all ages. Allele frequencies differed significantly between African Americans and whites at all but the APOA5 +56 C/G locus. Linkage disequilibrium among the loci was higher in whites and haplotype diversity lower: 6 haplotypes had estimated frequencies of more than 1% in African Americans, 5 in whites. Individually, all polymorphisms except APOC3 -2854 G/T showed significant associations with triglyceride levels in the full sample. However, genotype models including all 5 loci showed significant triglyceride associations for only 3 (APOC3 SstI, APOA5 -1131 T/C, and APOA5 +56 C/G); significant interactions among them indicated their effects were not independent. Neither APOC3 -2854 G/T nor APOA5 -3 A/G had significant effects when the other 3 loci were in the models. The EM algorithm was used to estimate haplotype frequencies and assign haplotype probabilities to individuals, which is conditional on their genotypes; individuals' haplotype probability vectors were then used as predictors in multilevel mixed models of longitudinal triglyceride profiles. Of haplotypes comprising, in order, APOC3 SstI and -2854 G/T and APOA5 -1131 T/C, -3 A/G, and +56 C/G, 3 were significantly associated with higher triglycerides, even after adjusting for multiple tests: GGTAG (P = .002), GTTAG (P < .0001), and CGCGC (P = .0002). Each GGTAG haplotype carried would be expected to raise triglyceride levels (relative to those of GTTAC homozygotes) by approximately 19 mg/dL, each GTTAG haplotype by approximately 15 mg/dL, and each CGCGC haplotype by approximately 7 mg/dL. Haplotypes comprising the 3 loci implicated by genotype analyses (SstI, -1131 T/C, and +56 C/G) were also tested: haplotypes C_C_C and G_T_G significantly raised triglycerides, even after adjustment for multiple comparisons (P < .002 for both), with each copy of C_C_C expected to raise triglycerides by approximately 7 mg/dL and each copy of G_T_G by approximately 15 mg/dL. Overall, our findings support those of others in associating specific polymorphisms and haplotypes in the APOA1/C3/A4/A5 gene cluster with higher serum triglyceride levels. However, the degree to which polymorphisms in the APOC3 and APOA5 genes may be independently associated with triglyceride levels remains to be determined.

Adolescent↗

PubMed2005

Gender-specific association of insertion/deletion polymorphisms in the nogo gene and chronic schizophrenia.

Nogo is a myelin-associated protein associated with neurite outgrowth and regeneration. A previous study has reported an association between an insertion/deletion polymorphism in schizophrenia. We tested for the distribution of the polymorphism and haplotypes of this and another insertion/deletion polymorphism in our population. We have also developed an assay combining allele-specific polymerase chain reaction (AS-PCR) and restriction fragment length polymorphism (RFLP) to simultaneously type these two insertion/deletion polymorphisms. There was a statistically significant difference at the allelic level for both the CAA (chi2 = 4.378, df = 1, P value = 0.036) and TATC (chi2 = 5.807, df = 1, P = 0.016) polymorphisms in the female subgroup, but not in males. With our genotyping method, we also determined the molecular haplotype. Within the female gender, odds ratio is at 1.57 (95% CI 1.05-2.37) for CAACAA-TATC and 1.40 (95% CI 0.55-3.60) for CAA-TATC, the two at-risk haplotypes. Odds ratio is 0.63 (95% CI 0.42-0.93) for the protective wildtype haplotype CAA-TATCTATC. Further study of these two polymorphisms to investigate functional significance and confirm gender-specific association should be carried out.

Adult↗

PubMed2004

Influence of GSTT1, mEH, CYP2E1 and RAD51 polymorphisms on diepoxybutane-induced SCE frequency in cultured human lymphocytes.

1,3-Butadiene (BD) is a common chemical in the human environment. Diepoxybutane (DEB) is the most reactive epoxide metabolite of BD. The aim of the present study was to evaluate the influence of polymorphisms in enzymes operating in DEB-metabolism (epoxide hydrolase mEH, CYP2E1 and GSTT1), as well as in the DNA-repair enzyme RAD51, on the frequency of sister chromatid exchange (SCE) induced by DEB in lymphocyte cultures from 63 healthy donors. Their genotypes were determined using PCR and restriction fragment length polymorphism (RFLP)-PCR techniques. The analysis of xenobiotic-metabolizing genes revealed that GSTT1 and CYP2E1 polymorphisms have an influence on DEB-induced SCE frequency. Individuals with the GSTT1 null genotype and CYP2E1 c2 variant allele heterozygotes were observed to have significantly higher SCE frequency than individuals with more common genotypes. A correlation between sensitivity to DEB and GSTT1 null genotype indicates that this pathway is a major detoxification step in DEB metabolism in whole-blood lymphocyte cultures, which has been shown in many studies. The analysis of combined polymorphisms indicated that, in the presence of GSTT1, a significantly higher DEB-induced SCE frequency is observed in the CYP2E1 c2 variant allele heterozygotes than in individuals with the most common CYP2E1 genotype. In the absence of GSTT1, however, the CYP2E1 polymorphism has no influence on DEB-induced SCEs. A significant difference was also observed between individuals characterized by low and high mEH activity, but only in subjects with the GSTT1 null genotype. Lack of GSTT1 resulted in higher SCE frequency in individuals with mEH high-activity genotypes than in individuals with mEH low-activity genotype. In the present study no statistically significant difference in DEB-induced SCEs was observed for the RAD51 polymorphism. The influence of GSTT1 genotype on SCE-frequency in RAD51 variant allele carriers was not analysed as all individuals in this group (except one person) had the GSTT1 gene present. Our study shows that the combined analysis of polymorphisms in metabolizing enzymes may lead to a better understanding of their contribution to an individual's susceptibility to DEB.

Base Sequence↗

PubMed2005

Investigation of the effect of brain-derived neurotrophic factor (BDNF) polymorphisms on the risk of late-onset Alzheimer's disease (AD) and quantitative measures of AD progression.

BDNF is a functional candidate gene for AD, owing to its role in neuronal development and survival. The Val66Met (G196A), along with another C270T polymorphism has been associated with AD, however, the effects seem to be inconsistent across studies. We examined the association of the G196A and C270T polymorphisms with sporadic late-onset AD (LOAD) in a large American White cohort of 995 AD cases and 671 controls and an American Black cohort of 64 AD cases and 45 controls. We also examined the association of these polymorphisms with quantitative measures of AD progression, including age at onset (AAO), disease duration and Mini-Mental State Examination (MMSE) scores. No significant difference in allele, genotype or estimated haplotype frequencies was observed between AD cases and controls within the American White and Black cohorts for the G196A and C270T polymorphisms. However, the frequency of the 196*A allele was significantly lower in American Black subjects compared to Whites. While MMSE scores were significantly lower in C270T/CT carriers compared to C270T/CC subjects only among American Blacks, no such effect was observed among American Whites. The BDNF polymorphisms did not affect AAO or disease duration measures in American Whites or Blacks. Our finding does not support any association between the BDNF/G196A or C270T polymorphism and the risk of sporadic LOAD among American Whites or Blacks. The significant effect of the C270T polymorphism observed on MMSE scores among American Blacks needs to be further explored in a larger cohort.

Aged↗

PubMed2006

Influence of lysosomal acid lipase polymorphisms on chromosome 10 on the risk of Alzheimer's disease and cholesterol metabolism.

Linkage analyses have identified a possible hot spot for a late-onset Alzheimer's disease (LOAD) risk gene on chromosome 10q21-22 and 10q25. It was also shown that cholesterol metabolism is involved in the pathogenic mechanisms of AD. The gene of lysosomal acid lipase (LIPA) is located next to the putative hot spot on chromosome 10. Its protein is involved in cholesterol metabolism and responsible for catalysing the hydrolysis of cholesteryl esters and triglycerides inside the lysosome. Previous publications reported controversial results on the role of LIPA polymorphisms on the risk of LOAD. We investigated two LIPA polymorphisms (rs1051338 and rs2297472) for their putative effect on the risk of LOAD in a homogenous sample of German origin. Genotypes of the investigated polymorphisms in AD patients and controls were compared. Also the effect of the LIPA gene polymorphisms on plasma cholesterol levels and 24S-hydroxycholesterol/cholesterol ratios on AD patients were investigated. None of the observed polymorphisms showed a significant influence on the risk of AD. We found that LIPA exon 2 polymorphism (rs1051338) influenced plasma 24S-hydroxycholesterol/cholesterol ratios in AD patients where carriers of the C/C allele presented with higher ratios than heterozygote carriers of the LIPA allele. Even though the biological function and gene location of LIPA on chromosome 10 suggest that LIPA might be a candidate for an AD risk gene, our results revealed that polymorphisms in LIPA did not influence the risk of AD in our study.

Aged↗

PubMed2005

Polymorphisms of heat shock protein 70 gene (HSPA1A, HSPA1B and HSPA1L) and schizophrenia.

The heat shock protein 70 (HSP70) is believed to be involved in the pathogenesis of schizophrenia with regards to neurodevelopment. An aberration in the HSP70 has been proposed in schizophrenia patients, suggesting that it is a candidate gene for schizophrenia. This study aimed to investigate the association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2 (HSPA1B) and schizophrenia. One hundred and sixty-one patients with schizophrenia and 165 controls were enrolled in the study. A polymerase chain reaction (PCR) with a restriction fragment length enzyme (RFLP) was used to genotype the HSPA1A, HSPA1L and HSPA1B polymorphisms. There were no significant differences in the allelic or genotype frequencies of the HSPA1A and HSPA1L polymorphisms between the schizophrenia patients and the controls, while there was a marginal difference in the genotype frequency of the HSPA1B polymorphisms, and a significant difference in the allelic frequency of the HSPA1B polymorphisms between the schizophrenia patients and the controls. There was no evidence of an association between the clinical variables and schizophrenia across the genotypes among the three HSP70 gene polymorphisms. These results suggest that a HSPA1B polymorphism might be related to the pathogenesis of schizophrenia at least in the Korean population. Therefore, larger studies from different ethnic groups should be performed to confirm these results.

Adult↗

PubMed2004

Genetic association between matrix metalloproteinase MMP-9 and MMP-3 polymorphisms and Japanese sporadic Alzheimer's disease.

Recent studies suggested that matrix metalloproteinases (MMPs) might play an important role in the pathophysiology of Alzheimer's disease (AD). MMP-9 and MMP-3 are reported to degrade amyloid beta and have several functional polymorphisms associated with other common diseases. Four common polymorphisms in each of MMP-9 and MMP-3 were examined in AD cases and normal control individuals. Common polymorphisms of MMP-9, rs3918248, rs2664538, rs2250889 and rs2274756 showed no association with risk for AD. We observed strong linkage disequilibrium (LD) between rs2664538 and rs2250889 in our Japanese samples. The polymorphisms of MMP-3; 5A/6A insertion polymorphism in the promoter, rs3025079, rs520540 and rs679620 also did not influence risk for AD. LD of the 5A/6A polymorphism with rs679620 was relatively strong. These results suggest that the common polymorphisms of MMP-9 and MMP-3 investigated here are not associated with AD.

Adult↗