Objective: To explore the relationship between the polymorphisms and haplotypes in the CETP gene and dyslipidemia among Xinjiang Kazak and Uygur residents.
Methods: A population status survey was performed from 2010 to 2011 in Kashgar Xinjiang Uygur and Kazak residents, stratified cluster sampling method was used to select Uygur, Kazak residents with abnormal blood lipid values (n=367 and 345, respectively) as the dyslipidemia groups, and to select residents with normal lipid values as control group from the same area (n=374 and 390, respectively). SNaPshot technology was applied to detect the DNA of CETP gene rs3764261, rs1800775, rs708272 and rs5882 loci in all selected residents, and linkage disequilibrium analysis and haplotype construction were performed.
Results: (1) In Uygur residents, the dyslipidemia risk of rs708272 CT (OR=0.64, 95%CI 0.46-0.91, P=0.01) and TT genotype (OR=0.60, 95%CI 0.40-0.91, P=0.02) was significantly lower than CC genotype. Dyslipidemia risk of rs3764261 GT (OR=0.55, 95%CI 0.40-0.74, P=0.00) and TT genotype (OR=0.47, 95%CI 0.28-0.78, P<0.01) was significantly lower than GG genetype. Dyslipidemia risk of the rs1800775 CC genotype was higher than AA genotype (OR=1.79, 95%CI 1.17-2.74, P=0.01). There was no statistical significance in CETP gene of the 4 genotype and allele frequency between the dyslipidemia and normal lipid groups in Kazak residents (all P>0.05). (2) In Uighur residents with dyslipidemia, HDL-C level was significantly higher in rs708272 TT genotype carriers than in CC and CT genotypes (all P<0.05) and in rs3764261 TT genotype carriers than in GG genotype carriers (P=0.008), while was significantly lower in rs1800775 CC genotype carriers with AA genotype carriers (P=0.008). (3) Linkage disequilibrium analysis showed that there was strong linkage disequilibrium between rs3764261 and rs708272 (D'=0.869, r(2)=0.869), rs1800775 and rs708272 (D'=0.845, r(2)=0.446) in Uighur residents, and there was strong linkage disequilibrium between rs3764261 and rs708272 (D'=0.963, r(2)=0.963), rs1800775 and rs708272 (D'=0.988, r(2)=0.630) in Kazak residents. (4) Significant differences were observed in frequency distribution of haplotype GACA(OR=0.579, 95%CI 0.388-0.864, P=0.006), GATA (OR=2.183, 95%CI 1.231-3.873, P=0.006), GCCA (OR=0.723, 95%CI 0.549-0.954, P=0.001), TATA (OR=0.723, 95%CI 0.549-0.954, P=0.021) and TATG (OR=0.601, 95%CI 0.429-0.841, P=0.002) in Uighur residents with normal or abnormal lipid profiles, while significant difference was observed in frequency distribution of haplotype GCCG (OR=1.961, 95%CI 1.207-3.188, P=0.005) in Kazak residents with normal or abnormal lipid profiles.
Conclusion: CETP genotype rs708272, rs3764261 and rs1800775 polymorphism is closely related to dyslipidemia and haplotype GACA, TATA and TATG will reduce the risk of dyslipidemia, while haplotype GATA, GCCA will increase the risk of dyslipidemia in Uygur residents. The four CETP polymorphisms are not related to the risk of dyslipidemia, but haplotype GCCG is related to increased risk of dyslipidemia in Kazakhs residents.