Dataset Information

RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans.

ABSTRACT: We previously found that plasma RBP4 levels were strongly associated with metabolic syndrome components. This study aimed to determine whether RBP4 variants are associated with the metabolic syndrome components and plasma RBP4 levels, and to investigate whether the associations between plasma RBP4 and the metabolic syndrome components are causal. Five tagSNPs were tested for their associations with plasma RBP4 levels and metabolic syndrome components in a population-based sample of 3,210 Chinese Hans. A possible causal relationship between plasma RBP4 levels and hypertriglyceridemia was explored by Mendelian randomization. Plasma RBP4 levels were significantly associated with rs10882273 (betaz -0.10SD[-0.17, -0.03], P = 0.0050), rs3758538 (betaz -0.13SD[-0.24, -0.02], P = 0.0249) in all participants, and with rs17108993 in Shanghai participants (betaz -0.19SD[-0.32, -0.05], P = 0.0061). The single nucleotide polymorphism (SNP) rs3758538 was significantly associated with hypertriglyceridemia (OR 0.62[0.45-0.85], P = 0.0026) and triglycerides (betaz -0.19SD[-0.30, -0.07], P = 0.001) in all participants. In Mendelian randomization analysis, the observed effect size of association between rs3758538 and hypertriglyceridemia was different from the expected effect size (P = 0.0213). This is the first study to show that the RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans. However, results of Mendelian randomization do not support the hypothesis that RBP4 levels are causally related to hypertriglyceridemia risk.

SUBMITTER: Wu Y

PROVIDER: S-EPMC2694346 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans.

Wu Ying Y Li Huaixing H Loos Ruth J F RJ Qi Qibin Q Hu Frank B FB Liu Yong Y Lin Xu X

Journal of lipid research 20090314 7

We previously found that plasma RBP4 levels were strongly associated with metabolic syndrome components. This study aimed to determine whether RBP4 variants are associated with the metabolic syndrome components and plasma RBP4 levels, and to investigate whether the associations between plasma RBP4 and the metabolic syndrome components are causal. Five tagSNPs were tested for their associations with plasma RBP4 levels and metabolic syndrome components in a population-based sample of 3,210 Chinese ...[more]

PMID: 19287041

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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.

Project description:BackgroundAlzheimer's disease (AD) has been associated with immune dysregulation in biomarker and genome-wide association studies (GWAS). GWAS hits include the genes encoding complement regulators clusterin (CLU) and complement receptor 1 (CR1), recognised as key players in AD pathology, and complement proteins have been proposed as biomarkers.Main bodyTo address whether changes in plasma complement protein levels in AD relate to AD-associated complement gene variants we first measured relevant plasma complement proteins (clusterin, C1q, C1s, CR1, factor H) in a large cohort comprising early onset AD (EOAD; n = 912), late onset AD (LOAD; n = 492) and control (n = 504) donors. Clusterin and C1q were significantly increased (p < 0.001) and sCR1 and factor H reduced (p < 0.01) in AD plasma versus controls. ROC analyses were performed to assess utility of the measured complement biomarkers, alone or in combination with amyloid beta, in predicting AD. C1q was the most predictive single complement biomarker (AUC 0.655 LOAD, 0.601 EOAD); combining C1q with other complement or neurodegeneration makers through stepAIC-informed models improved predictive values slightly. Effects of GWS SNPs (rs6656401, rs6691117 in CR1; rs11136000, rs9331888 in CLU; rs3919533 in C1S) on protein concentrations were assessed by comparing protein levels in carriers of the minor vs major allele. To identify new associations between SNPs and changes in plasma protein levels, we performed a GWAS combining genotyping data in the cohort with complement protein levels as endophenotype. SNPs in CR1 (rs6656401), C1S (rs3919533) and CFH (rs6664877) reached significance and influenced plasma levels of the corresponding protein, whereas SNPs in CLU did not influence clusterin levels.ConclusionComplement dysregulation is evident in AD and may contribute to pathology. AD-associated SNPs in CR1, C1S and CFH impact plasma levels of the encoded proteins, suggesting a mechanism for impact on disease risk.

Dataset Information

RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans.

Publications

RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans.

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