Abstract
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.
Highlights
The goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population
There was no significant difference in systolic blood pressure (SBP), diastolic blood pressure (DBP), gender, age, and GLU between the case and control groups (Additional file 1: Table S1)
In the stage I study, we found that the Single nucleotide polymorphisms (SNPs) rs2228570 statistically correlated with an increased risk of dyslipidemia; after adjusting for confounding factors, the odds ratios (ORs) with 95% confidence interval (CI) of the additive, dominant, and recessive models were 1.255 (1.118–1.409) (P < 0.001),1.384 (1.136–1.6)(P = 0.001) and 1.356 (1.1–1.671)(P = 0.004) (Table 1)
Summary
The goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population. Low vitamin D status has been reported to be correlated with an increased risk of hyperlipidemia [1, 2]. Vitamin D likely increases serum calcium by enhancing intestinal calcium absorption. This elevated calcium level reduces serum triglycerides by suppression of hepatic triglyceride formation and secretion [6]. The lowered level of PTH may reduce serum triglycerides by increasing their peripheral uptake. Another potential mechanism to explain the association between 25(OH) D and triglycerides would be through insulin resistance. In cases of vitamin D deficiency, the risk of insulin resistance increases, which is associated with elevated levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides [7]
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