Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain.
J Lipid Res. 2010 Sep;51(9):2798-807. doi: 10.1194/jlr.P005199. Epub 2010 Jun 25.
Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors.
全基因组关联研究表明,胆固醇酯转移蛋白 (CETP) 单核苷酸多态性 (SNP) 与高密度脂蛋白胆固醇 (HDL-C) 浓度的相关性比全基因组中的任何其他基因座都要强。然而,基因-环境相互作用在临床应用中仍知之甚少。我们研究了 CETP SNPs 与饮食脂肪摄入、地中海饮食依从性、饮酒、吸烟、肥胖和糖尿病之间的基因-环境相互作用,在来自地中海人群的 4210 名高心血管风险患者中对 HDL-C 进行了研究。我们重点研究了部分连锁不平衡的 -4,502C>T 和 TaqIB SNPs(D'=0.88;P<0.001)。它们与更高的 HDL-C 独立相关(P<0.001);当考虑其双型时,这种具有临床意义的相关性更大(TT/B2B2 比 CC/B1B1 高 14%)。未观察到基因-基因相互作用。我们还分析了这些 SNP 与血压的关联,未发现具有临床意义的关联。在确定 HDL-C 浓度时,这些 SNP 与肥胖、糖尿病和吸烟之间没有统计学显著的相互作用。同样,酒精、饮食脂肪和地中海饮食的依从性与 CETP 变异(独立或作为双型)在确定 HDL-C 方面没有统计学上的相互作用。总之,CETP SNPs 与 HDL-C 的强相关性不受饮食或其他环境因素的统计学修饰。