Vitamin D receptor genetic polymorphism is significantly associated with decreased risk of hypertension in a Chinese Han population.
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ABSTRACT:
SUBMITTER: Jia J
PROVIDER: S-EPMC8031604 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChR) or other functional molecules in the postsynaptic membrane at the neuromuscular junction. Vitamin D (VD) has a number of pluripotent effects, which include immune-regulation and bone metabolism. The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to a vitamin D receptor (VDR). In the study, we undertook a case-control study to explore the association between VDR gene polymorphism and the susceptibility and severity of MG patients. Four hundred and eighty MG patients and 487 healthy controls were included and gene polymorphisms of VDR were determined with improved multiplex ligation detection reaction technique and SNPscanTM technique. MG patients were classified into subgroups by essential clinical features and by a comprehensive classification. The frequencies of alleles and genotypes were compared between the MG group and the control group, between each MG subgroup and the control group, and between each pair of MG subgroups. There were no significant differences in frequencies of alleles and genotypes between MG patients and healthy controls, between MG subgroups and healthy controls, or between each pair of MG subgroups in the analysis of subgroups classified by essential clinical features (onset age, gender, thymoma, AChRAb positivity, onset involvement) and the maximal severity (modified Oosterhuis score). In the analysis of subgroups with a comprehensive classification, the frequencies of alleles and genotypes in rs731236 showed significant differences between adult non-thymoma AChRAb negative MG subgroup and the control group, as well as the adult non-thymoma AChRAb positive MG group. In the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients, although this needs further confirmation.
| S-EPMC7900549 | biostudies-literature
Project description:BackgroundThe goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population.MethodsThree tag single nucleotide polymorphisms (SNPs) (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan assays to determine VDR SNP associations with dyslipidemia. We genotyped 877 cases of dyslipidemia from a normotensive, non-diabetes mellitus population and 1822 non-dyslipidemia subjects in a stage I study. In a follow-up stage II study, we included a larger sample of 3124 controls and 1679 cases with dyslipidemia. Finally, we explored the potential molecular mechanism for the SNP associations using molecular modeling analysis.ResultsWe found a significant association between SNP rs2228570 and dyslipidemia in the additive (adjusted odds ratio (OR) = 1.255, 95% Confidence Interval (CI) = (1.118-1.409), P < 0.001), dominant (OR = 1.384, 95% CI = 1.384 (1.136-1.6), P = 0.001) and recessive models (OR = 1.356, 95%CI = 1.1-1.671, P = 0.004) in stage I. We further established that the rs2228570 variant was significantly associated with dyslipidemia in the additive (adjusted OR = 1.146, 95% CI = 1.053-1247, P = 0.002), dominant (OR = 1.184, 95%CI =1.018-1.376, P = 0.028) and recessive models (OR = 1.209, 95%CI = 1.064-1.374, P = 0.004) in stage II. The TT genotype was significantly higher (4.93 ± 0.75 mmol/L) compared to the TC (4.67 ± 0.47 mmol/L) or CC (4.66 ± 0.44 mmol/L) genotype (P = 0.01) in cases with elevated low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the cases with the TT genotype had significantly lower serum 25(OH)D levels (18.43 ± 5.04 ng/ mL) compared to the TC (26.24 ± 4.16 ng/mL) and CC (36.76 ± 8.10 ng/ mL) genotypes (P < 0.001). Multivariable linear regression analysis indicated that the rs2228750 genotype significantly correlated with serum low-density lipoprotein-C (LDL-C) levels in cases with dyslipidemia. Using molecular modeling analysis, we further found that the rs2228570 variant changed the structure and the stability of VDR and altered the binding energy of its ligand.ConclusionsThe VDR rs2228570 variant may increase susceptibility to dyslipidemia in the Chinese Han population.
| S-EPMC6098609 | biostudies-literature
Project description:Hypertension, including secondary and essential hypertension (EH) variants, is a multifactorial disease, affecting more than one billion people worldwide. Secondary hypertension results from mutations in the putative gene KLHL3 (Kelch-like protein 3); however, it has not been reported whether the KLHL3 gene polymorphisms are associated with EH. Here, we investigated the association between KLHL3 (rs2301708 and rs7444370) polymorphisms and EH in the Chinese Han population.This case-control study included 522 subjects-260 patients with EH and 262 normotensive controls matched for age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), and levels of Na, K, and Cl. The distribution of functional rs2301708 and rs7444370 polymorphisms within the KLHL3 gene was assessed through polymerase chain reaction (PCR) and restriction-fragment length polymorphism (RFLP).There was no significant difference in allelic and genotypic frequencies of KLHL3 rs2301708 between the EH and normotensive groups; however, the rs7444370 T allele and CT genotype in females was significantly associated with a protective effect against EH (P = .001, P = .002; P = .019, P = .052), and the haplotype CT of rs2301708 and rs7444370 among females in the EH group was less than in the normotensive group (P = .000; P = .007).The KLHL3 rs7444370 variant could be a protective factor in the pathogenesis of females' EH.
| S-EPMC6531237 | biostudies-literature
Project description:BACKGROUND:Vitamin D receptor (VDR) is involved in multiple immune-mediated disorders including oral lichen planus (OLP). This study investigated the association between VDR gene polymorphisms and the risk of OLP. METHODS:In total, 177 OLP patients and 207 healthy participants were recruited from the Affiliated Hospital of Stomatology, Nanjing Medical University. Eight single nucleotide polymorphisms (SNPs: rs731236, rs739837, rs757343, rs2107301, rs2239185, rs7975232, rs11574129 and rs11568820) in the VDR gene were selected and genotyped. RESULTS:The results showed that OLP risk was increased in subjects with the rs2239185 TT genotype (Recessive model: adjusted Odd ratio(OR)?=?2.68, 95% Confidence interval(CI)?=?1.28-5.62, P?=?0.009) and rs7975232 CC genotype (Recessive model: adjusted OR?=?2.25, 95% CI?=?1.10-4.58, P?=?0.026). Moreover, rs2239185 and rs7975232 (P?< 0.01) showed significant cumulative effects on OLP risk.Haplotype analysis showed that the CC haplotype (rs2239185-rs7975232) was associated with an increased risk of OLP (OR?=?3.11, 95% CI?=?1.42-6.83, P?=?0.005), compared with the AC haplotype. CONCLUSION:The rs2239185 and rs7975232 variants of VDR may influence OLP susceptibility, and VDR gene polymorphisms may be candidate susceptibility regions for OLP in a Chinese Han population.
| S-EPMC6993400 | biostudies-literature
Project description:Osteoporosis is a polygenic disorder and has been demonstrated to be associated with ~30 candidate genes, the majority of which have also been implicated in the regulation of bone mineral density (BMD). Vitamin D receptor (VDR) is the candidate gene that has been most extensively studied. Certain studies have reported that the VDR single nucleotide polymorphism ApaI is associated with the risk of osteoporosis in Caucasian and African women. However, this association has not yet been studied in postmenopausal Han Chinese women in the Xinjiang area. In the present study, ApaI polymorphisms of VDR were defined by polymerase chain reaction-restriction fragment length polymorphism, in order to analyze the distribution of ApaI polymorphisms in postmenopausal Han Chinese women from Xinjiang. BMD was measured by dual energy X-ray absorptiometry at the lumbar spine (L2-4), Ward's triangle, great trochanter and femoral shaft. A total of 336 women were included in this study. The genotype distribution of ApaI was consistent with the Hardy-Weinberg equilibrium (all P>0.05). There were no significant differences in ApaI genotype frequencies between the 90 cases in the osteoporosis group and 246 cases in the non-osteoporosis group (P=0.946). Meanwhile, it was identified that BMD values of the tested locations were negatively correlated with age (P<0.05) and positively correlated with body mass index (BMI; P<0.05). On further attribution risk analysis, BMD was identified as a risk factor [odds ratio (OR): 0.464, 95% confidence interval (CI): 0.372-0.580, P=0.001] and BMI a protective factor (OR: 1.502, 95% CI: 1.008-2.240, P=0.032) in osteoporosis. When BMD was adjusted for confounding factors including age and BMI, it was observed that the ApaI polymorphism was not associated with BMD at the sites tested (P>0.05). In conclusion, the present study identified no significant association of the common VDR polymorphism ApaI with BMD at several skeletal sites in postmenopausal Han Chinese women in the Xinjiang area. Age was negatively correlated with BMD at different sites and identified as a risk factor; while BMI was positively correlated with BMD and identified as a protective factor.
| S-EPMC6256115 | biostudies-other
Project description:BACKGROUND: Toll-like receptors (TLRs), as major innate immune mediators, may be involved in clearance of cerebral amyloid-? (A?) deposits. Recently, a novel TLR9 signaling pathway has been uncovered, which is functionally associated with the immune inflammatory response and reducing A? burden in Alzheimer's disease (AD) mice. Therefore, TLR9 might represent a reasonable functional candidate gene for AD. FINDINGS: Our study investigated 1,133 sporadic late-onset AD (LOAD) and 1,159 healthy controls matched for sex and age in a large Han Chinese population. One selected functional rs187084 polymorphism within the TLR9 gene was genotyped by polymerase chain reaction-ligase detection reaction in a case-control associated study. The TLR9 rs187084 variant homozygote GG was significantly associated with a decreased LOAD risk after adjusting for age, gender, and ApoE ?4 status by logistic regression analysis (P?=?0.035). Our result showed significant evidence of the interaction of ApoE ?4 with rs187084. When we further stratified our data by the ApoE ?4 status, we detected significant differences in the genotype and allele distributions of rs187084 between LOAD patients and controls in ApoE ?4 carriers (P?<?0.001, P?=?0.003, respectively). Moreover, we examined TLR9 expression in peripheral blood monocytes by flow cytometry, and the GG genotype of the TLR9 rs187084 polymorphism was associated with a higher TLR9 expression than two other genotypes in LOAD patients. CONCLUSION: Our findings support the hypothesis that the TLR9 polymorphism may modify LOAD risk in the Han Chinese population.
| S-EPMC3765501 | biostudies-literature
Project description:BackgroundStudies investigated the associations between four Vitamin D receptor (VDR) common variations and interactions of gene-environment factors and atopic dermatitis (AD) in Chinese population are few.MethodsIn this case-control study, 400 AD patients and 400 controls were genotyped for the FokI, TaqI, BsmI and ApalI variations of VDR genes by restriction fragment length polymorphism analysis. The associations between VDR genes and AD were assessed by univariate and multivariate logistic regression. The interactions between VDR genes and some risk factors were also explored using cross-over analysis. The corresponding odds ratio (ORs) and 95% confidence intervals (CI) were also calculated.ResultsThe FoKI rs2228570 polymorphism was significantly associated with an increased risk of atopic dermatitis in the co-dominant model (OR=2.93, 95% CI: 1.78-4.82. P=0.000), recessive model (OR=2.67, 95% CI: 1.68-4.26, P=0.000) and dominant model (OR=1.38, 95% CI: 1.04-1.84, P=0.028), and allele model. No significant associations were found among TaqI, BsmI and ApalI polymorphism and AD. The C-A-T-C and C-G-T-T haplotypes significantly increased the risk of atopic dermatitis. For rs2228570, the increased effects were more evident in the subgroups of age ≤8-month, cow milk and mixed, and keeping pet. Interactions between rs2228570 gene polymorphism and family history, age >8, and keeping pet increased the AD risk. The rs2228570 C allele decreased the relative mRNA expression.ConclusionThe FokI rs2228570 C allele of VDR gene could be a risk candidate gene for AD. Interactions between FokI polymorphism and family history and some behaviors may increase the risk of AD.
| S-EPMC8435479 | biostudies-literature
Project description:BackgroundAnimal study found that soluble guanylate cyclase (sGC) plays an important role in development of hypertension (HT) by affecting the NO-sGC-CGMP signaling pathway. This study aims to evaluate the association of sGC with essential hypertension (EH) in the Han Chinese population.MethodsThis case-control study included 2,012 hypertensive cases and 2,210 controls, and 6 tagging single nucleotide polymorphisms (SNPs) were selected (rs3806777, rs3806782, rs3796576 and rs7698460 in GUCY1A3, as well as rs2229202 and rs1459853 in GUCY1B3). Then the association of the six SNPs with EH was further evaluated in this study.ResultsThe results indicated that the A/A genotype of rs1459853 in GUCY1B3 was associated with higher HT risk, and the odds ratio (OR) of its recessive model was 1.191 (P=0.044). After adjusting for covariates, the association was still significant. Further stratification analyses showed that rs1459853 in non-drinking subjects and rs7698460 in women were associated with EH. In the follow-up study, rs1459853 were related to increased HT risk in men and smoker subjects. In adolescents, rs2229202 that in GUCY1B3 had significant association with prehypertension (Pre-HT), HT, and prehypertension with hypertension (Pre-HT + HT). After adjusted for covariates, the association was remaining significant. And in girls, rs3806782 was significantly connected with HT and Pre-HT + HT.ConclusionsOverall, our findings suggest that sGC may contribute to the genetic susceptibility to EH, and it was validated for the first time in adolescents.
| S-EPMC6944586 | biostudies-literature
Project description:The relationship between CYP17A1 genetic polymorphisms and essential hypertension (EH) remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with EH in Han and Uighur populations in China. A Han population including 558 people (270 EH patients and 288 controls) and a Uighur population including 473 people (181 EH patients and 292 controls) were selected. Five single-nucleotide polymorphisms (SNPs) (rs4919686, rs1004467, rs4919687, rs10786712, and rs2486758) were genotyped using real-time PCR (TaqMan). In the Uighur population, for the total and the men, rs4919686, rs4919687 and rs10786712 were found to be associated with EH (rs4919686: P?0.02, rs4919687: P?0.002, rs10786712: P?0.004, respectively). The difference remained statistically significant after the multivariate adjustment (all P<0.05). The overall distributions of the haplotypes established by SNP1-SNP3, SNP1-SNP4, SNP1-SNP3-SNP5 and SNP1-SNP4-SNP5 were significantly different between the EH patients and the control subjects (for the total: P=0.013, P=0.008, P=0.032, P=0.010, for men: P<0.001, P=0.001, P=0.010, P=0.00). In the Han population, for men, rs2486758 was found to be associated with EH in a recessive model (P=0.007); the significant difference was not retained after the adjustment for the covariates (date not shown). The A allele of rs4919686 could be a susceptible genetic marker, and the T allele of rs10786712 could be a protective genetic marker of EH. The AC genotype of rs4919686, the AG genotype of rs4919687 and the TT genotype of rs10786712 could be protective genetic markers of EH.
| S-EPMC4657820 | biostudies-literature
Project description:BackgroundCYP17A1 gene encodes P450c17 proteins, which is a key enzyme that catalyzes the formation of sex hormones. Many clinical studies showed that sex hormones levels play an important role in the pathogenesis of coronary artery disease (CAD). However, the relationship between CYP17A1 genetic polymorphisms and CAD remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with CAD in a Han population of China.MethodsA total of 997 people include 490 patients and 507 controls were selected for the present study. Five single-nucleotide polymorphisms (SNPs) (rs4919686, rs1004467, rs4919687, rs10786712, and rs2486758) were genotyped by using the real-time PCR (TaqMan) method.ResultsFor men, the rs10786712 was found to be associated with CAD in a recessive model (P=0.016), after adjustment of the major confounding factors, the significant difference was retained (OR=1.644, 95% confidence interval [CI]: 1.087-2.488, P=0.019). For women, the rs1004467 was also found to be associated with CAD in a dominant model (P=0.038), the difference remained statistically significant after multivariate adjustment (OR=1.623, 95% CI: 1.023-2.576, P=0.040). The distribution of rs4919687 genotypes showed a significant difference between CAD and control participants in a recessive model (P=0.019), the significant difference was retained after adjustment for covariates (OR=0.417, 95% CI: 0.188-0.926, P=0.032).ConclusionRs1004467, rs4919687, rs10786712 of CYP17A1 gene are associated with CAD in Han population of China. The TT genotype of rs10786712 could be a protective genetic marker of CAD in men. The CC genotype of rs1004467 and the AA genotype of rs4919687 could be risk genetic markers of CAD in women. However, large sample size study including other SNPs of CYP17A1 should be performed in future studies.
| S-EPMC4359393 | biostudies-literature