CETP基因多态性及其单体型与新疆维吾尔族、哈萨克族人群血脂异常的相关性

Association between CETP polymorphisms and haplotypes with dyslipidemia in Xinjiang Uygur andKazak residents

目的探讨新疆地区维吾尔族、哈萨克族人群胆固醇酯转运蛋白（CETP）基因多态性及其单体型与血脂异常的关系。方法2010至2011年对新疆喀什地区维吾尔族和哈萨克族人群现况调查的基础上，采用分层整群抽样的方法分别选取维吾尔族、哈萨克族血脂异常者367、345例作为该民族血脂异常组，并从同一地区和民族中分层随机抽取血脂正常个体374、390例作为该民族对照组；利用SNaPshot技术检测抽提出所有研究对象的DNA中CETP基因rs3764261、rs1800775、rs708272和rs5882位点基因型，并进行连锁不平衡分析和单体型构建。结果（1）维吾尔族人rs708272的CT（OR＝0.64，95%CI 0.46～0.91，P＝0.01）、TT基因型携带者（OR＝0.60，95%CI 0.40～0.91，P＝0.02）发生血脂异常的风险均低于CC基因型；rs3764261的GT（OR＝0.55, 95%CI 0.40～0.74，P〈0.01）、TT基因型携带者（OR＝0.47，95%CI 0.28～0.78，P〈0.01）发生血脂异常的风险均低于GG基因型；rs1800775的CC基因型携带者发生血脂异常的风险高于AA基因型（OR＝1.79, 95%CI 1.17～2.74，P＝0.01）。哈萨克族人CETP基因该4个位点基因型和等位基因频率在两组间差异均无统计学意义（P均〉0.05）。（2）维吾尔族血脂异常组rs708272位点的TT基因型高密度脂蛋白胆固醇（HDL-C）水平均高于CC、CT基因型（P均〈0.05）；rs1800775位点的CC基因型HDL-C水平低于AA基因型（P＝0.008）；rs3764261位点的TT基因型HDL-C水平高于GG基因型（P＝0.008）。（3）连锁不平衡分析显示，维吾尔族人群rs3764261与rs708272间（D＇＝0.869，r2＝0.398）、rs1800775与rs708272间（D＇＝0.845，r2＝0.446）呈强连锁不平衡；哈萨克族人群rs3764261与rs708272间（D＇＝0.963，r2＝0.372），rs1800775与rs708272间（D＇＝0.988，r2＝0.630）呈强连锁不平衡。（4）维吾尔族单体型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）和TATG （OR＝0.601, 95%CI 0.429～0.841, P＝0.002）在两组间频率分布差异有统计学意义；哈萨克族单体型GCCG （OR＝1.961, 95%CI 1.207～3.188, P＝0.005）在两组间频率分布差异有统计学意义。结论CETP基因rs708272、rs3764261和rs1800775位点多态性与新疆维吾尔族人群血脂异常密切相关，且单体型GACA、TATA和TATG会降低维吾尔族个体患血脂异常的风险；而GATA、GCCA则会增加维吾尔族个体患血脂异常的风险；CETP该4个位点多态性与新疆哈萨克族人群血脂异常关系不密切，但单体型GCCG会增加哈萨克族个体族患血脂异常的风险。

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 O. 46 - 0. 91, P = 0. 01 ） and TT genotype （ OR = 0. 60,95%o CI O. 40 - 0. 91, P = 0. 02 ） was significantly lower than CC genotype. Dyslipidemia risk of rs3764261 GT （OR=0.55, 95%oCI0.40 -0.74, P=0.00） and TT genotype （OR=0.47, 95%oC1 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 T genotype carders 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, r2 = 0. 869）, rs1800775 and rs708272 （ D = 0. 845, r2 = 0. 446） in Uighur residents, and there was strong linkage disequilibrium between rs3764261 and rs708272 （D＇ = 0. 963, r2 = 0. 963 ）, rs1800775 and rs708272 （D＇ =0. 988, r2 =0. 630） in Kazak residents. （4） Significant differences were observed in frequency distribution of haplotype GACA （ OR = 0. 579, 95 %o C10. 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 O. 549 -0. 954, P = 0. 001 ）, TATA （ OR = 0. 723, 95% CI O. 549 - 0. 954, P = 0. 021 ） and TATG （ OR = 0. 601, 95% CI 0. 429-0. 84l, 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. 961,950/0 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.