双生子中脂蛋白脂酶基因S447X突变与血脂、血压的关联和连锁分析

Association and linkage analysis between the S447X polymorphism of LPL gene and serum lipids, blood pressures in twins

目的在以一般人群为基础的中国成人双生子中探讨脂蛋白脂酶(LPL)基因S447X突变是否和血脂、血压有关联和连锁。方法基于双生子登记系统,对双生子进行问卷、体检、生化指标测定以及S447X突变的检测。按性别分层,分别进行S447X突变与甘油三酯(TG)、高密度脂蛋白(HDL)、收缩压(SBP)、舒张压(DBP)及其异常之间的单因素和控制混杂因素后的多因素关联分析。用基于Halesman-Elston回归的非参数同胞对连锁分析方法,在异卵双生子(DZ)中进行该突变位点和血脂、血压的连锁分析。结果在962对成人双生子中,S447X突变等位基因的频率为8.6%;TG、HDL、SBP和DBP的遗传度分别为57%、68%、46%和44%;单因素和多因素关联分析显示,在女性双生子中,S447X突变和TG下降12.9%显著相关,也和SBP下降2.7mm Hg(1mm Hg=0.133kPa)、DBP下降1.8mm Hg显著相关。而且,S447X突变和高TG异常、低HDL异常及高血压的发生风险降低也呈显著相关,OR值分别为0.38(95%CI0.20～0.76)和0.49(95%CI0.29～0.81)和0.47(95%CI0.25～0.86)。结论在女性双生子中,S447X突变和血脂改善及血压降低相关,但在男性双生子中没有发现这种关联。也没有发现S447X突变位点和血脂及血压性状位点的连锁关系。因此,S447X突变和血脂及血压的关系可能是由于该突变和其它调节血脂和/或血压的功能性突变存在连锁不平衡所致。

Objective： To investigate the association and linkage between the S447X polymorphism of LPL gene and serum lipids, blood pressures in the general population-based twin cohort of China. Methotis： The twin subjects were collected based on the twin registry system of China. All twins were investigated by a standard questionnaire and physical examinations. PCR - RFLP method was used to detect the genotypes of S447X. Stratified by gender, the associations of S447X polymorphism with the serum lipids （ TG, HDL）, blood pressures （ SBP, DBP） and their abnormalities were analyzed by univariate and multivariate methods. The Halesman - Elston regression based non-parameter linkage analysis was applied in the DZ twins. Results： A total of 962 adult twin pairs were analyzed and the frequency of 447X allele was 8.6%. The heritabilities of TG, HDL, SBP and DBP were 57% , 68% , 46% and 44% , respectively. In female twins, univariate and multivariate association analyses showed that the 447X allele was associated with the 12.9% decrease of TG and 2.7 mm Hg （1 mm Hg =0. 133 kPa） decrease of SBP, 1.8 mm Hg decrease of DBP. Also in female twins, 447X allele was associated with the lower risks of high TG dyslipidaemia, low HDL dyslipidaemia and hypertension, with the odds ratios 0.38 （95% CI： 0.20 - 0.76 ）, 0.49 （95 % CI： 0.29 - 0.81 ） and 0.47 （ 95 % CI： 0.25 - 0.86 ）, respectively. Conclusion： This study showed significant associations between the S447X polymorphism of LPL gene and the improved serum lipids, decreased blood pressures in the female twins. But no associations were observed in male twins, and no linkage evidences were found between the locus site of S447X polymorphism and the trait loci of serum lipids, blood pressures. So the associations maybe caused by the other functional SNPs within or near LPL gene, which might be in significant linkage disequilibrium with 447X mutation.