Genetic Polymorphisms of CD36 Associated With Metabolic Syndrome in Chinese Han Population: A Nested Case-Control Study

Aims: CD36 , an important gene involved in cholesterol and fatty acid metabolism,, has been associated with many metabolic-related traits, including diabetes, hypertension, and obesity in different populations. However, the association of this gene with metabolic syndrome (MS) has not been well-studied. We aimed to investigate the association of CD36 with the risk of MS and longitudinal changes of its components in among participants of the Rural Chinese Cohort Study (RCCS). Materials and Methods: The RCCS enrolled 20,194 participants aged 2 18 years old between July of 2007 and August of 2008. A total of 17,265 participants (response rate 85.5%) were examined in the follow-up survey between July of 2013 and October of 2014. During the six years, 729 new incident cases of MS were ascertained. We conducted a nested case-control study within the RCCS. Specifically, 408 MS randomly cases and 408 one-to-one matched controls were included in the current study. In addition to follow-up time, non-MS controls were matched to MS cases on age, gender, marital status, and residence village. Human genomic DNA was extracted using a standard method from blood samples collected at the baseline. After quality control, 4 single nucleotide polymorphisms (SNPs) within the CD36 were successfully genotyped. MS was defined according to the 2009 criteria proposed by IDF and AHA/NHLBI. Multivariate conditional logistic regression was used to determine additive associations of SNPs and SNP-haplotype with MS adjusting for body mass index (BMI), smoking, drinking, and physical activity at baseline. Multivariate linear regression models were conducted among the control group to examine association of SNPs and SNP-haplotypes with MS components, controlling for age, gender, BMI, smoking, drinking and physical activity. Multiple testing was corrected by false positive discovery rate (FDR) method. Results: Two SNPs, rs7755 and rs1049673, were associated with risk for MS. Per minor allele increase in rs7755 and rs1049673 was associated with 2.29 (95% confidence interval [CI]: 1.24-4.24, p =0.008) and 2.30 (95% CI: 1.24-4.26, p =0.008) times higher odds of MS, respectively. In addition, rs1194197 was associated with changes of triglycerides level (β=0.151, p =0.014), and rs7755 (β=-0.065, p =0.028) and rs1049673 (β=-0.067, p =0.025) were associated with changes of high density lipoprotein cholesterol in the control group. One haplotype of the four SNPs, AGAG, was associated with the change of waist circumference (β=-1.773, p =0.048). Conclusions: We identified important SNPs and SNP-haplotypes of the CD36 associated with MS and changes of MS components in a Han Chinese population.