Padmaja N, Ravindra Kumar M, Soya S S, Adithan C
Pharmacogenomics Laboratory, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry-605 006, India.
Clin Chim Acta. 2007 Jan;375(1-2):140-6. doi: 10.1016/j.cca.2006.06.031. Epub 2006 Jul 1.
Cholesteryl ester transfer protein (CETP) is involved in a key pathway of reverse cholesterol transport implicated in atherosclerosis and coronary heart disease. CETP gene is known to have many single nucleotide polymorphisms which have been associated with CETP activity and plasma high density lipoprotein cholesterol (HDL-C) concentrations. No data on the prevalence of these polymorphisms and their phenotypic association is available in South Indian population.
Three CETP polymorphisms: TaqIB, -629C/A and I405V were studied in 171 healthy volunteers from Tamilnadu, a major population of South India. Subjects were clinically examined and lipid profile was estimated. Genotyping was performed by PCR-RFLP and genotype frequencies estimated.
The allele frequencies of TaqIB: B1 allele was 0.51; -629C/A: C allele was 0.36; and that of I405V: I allele was 0.47. Study of association between these three polymorphisms and plasma lipid concentrations revealed no significant differences in lipid parameters between genotypes. A gender based subgroup analysis revealed a significant increase in HDL-C in men with B2B2 genotype and decrease in TG in B1B2 genotype. Analysis of the combined effect of multiple mutant genotypes revealed that as the number of mutant genotypes increased, the concentrations of low density lipoprotein-cholesterol (LDL-C), HDL-C and total cholesterol (TC) increased whereas that of triglyceride (TG) decreased in the group of three mutant genotypes significantly.
The frequency of B2 and A alleles of TaqIB and -629C/A polymorphisms were highest in Tamilian population when compared to other major ethnic groups while that of V allele of I405V polymorphism is between Caucasians and African Americans. Taq1B polymorphism was associated with HDL-C and TG concentrations only in men. Combination of these three polymorphisms was significantly associated with lipid profile than the individual polymorphisms.
胆固醇酯转运蛋白（CETP）参与逆向胆固醇转运的关键途径，该途径与动脉粥样硬化和冠心病有关。已知CETP基因有许多单核苷酸多态性，这些多态性与CETP活性和血浆高密度脂蛋白胆固醇（HDL-C）浓度相关。在南印度人群中，尚无关于这些多态性的患病率及其表型关联的数据。
对来自印度南部主要人群泰米尔纳德邦的171名健康志愿者进行了三种CETP多态性研究：TaqIB、-629C/A和I405V。对受试者进行临床检查并评估血脂谱。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型并估计基因型频率。
TaqIB的等位基因频率：B1等位基因为0.51；-629C/A：C等位基因为0.36；I405V的等位基因频率：I等位基因为0.47。对这三种多态性与血浆脂质浓度之间的关联研究表明，各基因型之间的脂质参数无显著差异。基于性别的亚组分析显示，B2B2基因型男性的HDL-C显著升高，B1B2基因型男性的甘油三酯（TG）降低。对多个突变基因型的联合效应分析表明，在三种突变基因型组中，随着突变基因型数量的增加，低密度脂蛋白胆固醇（LDL-C）、HDL-C和总胆固醇（TC）的浓度升高，而TG浓度显著降低。
与其他主要种族群体相比，泰米尔人群中TaqIB和-629C/A多态性的B2和A等位基因频率最高，而I405V多态性的V等位基因频率介于白种人和非裔美国人之间。Taq1B多态性仅在男性中与HDL-C和TG浓度相关。这三种多态性的组合与血脂谱的关联比单个多态性更为显著。
