13种参与血管调节基因位点与中国人高血压病的连锁分析

Linkage analysis of 13 vasoactivity-regulating short tandem genes loci in essential hypertension in Chinese

目的 连锁分析肾素 血管紧张素系、内皮素系、一氧化氮合酶、肾上腺素受体等 13种参与血管调节基因位点与中国人高血压病关系。方法 在 13种参与血管调节的候选基因附近 ,各选1个短串联重复序列 (STR)作为遗传标记 ,应用荧光标记引物 基因扫描及分型技术 ,对 95个汉族高血压病家系 4 77个成员进行STR多态性位点与高血压病连锁分析。统计用GENEHUNTER软件包进行最大优势对数记分 (Lod)法、两点非参数连锁 (NPL)分析及传递不平衡检验 (TDT)。结果 用TDT法发现D1S16 78、D3S174 4、D4S16 0 4、D13S80 0、D7S4 83、D8S2 5 5等 6个位点 0 0 1<P <0 0 5 ,其余位点P≥0 0 5 ;所有位点NPL分析P >0 0 5 ,最大Lod值 <- 1。结论 TDT分析是很敏感的检验方法 ,有 6个位点存在传递不平衡 ,对这些位点附近的基因与高血压病的关系值得关注 ,但用该法似获更小P值才能减少假阳性。用 3种统计方法均未发现其余位点与高血压病连锁。

Objective To investigate whether linkage between essential hypertension (EH) and genetic loci near renin angiotensin system, endothelin system , nitric oxide synthase , adrenergic receptor genes in Chinese Methods Linkage analysis of thirteen candidate gene loci and EH was performed in 95 Chinese nuclear families including 477 subjects using a technique of fluorescence based gene scan with DNA short tandem repeat The markers were selected on the chromosomal regions containing candidate genes regulating vasoactivity GENEHUNTER package were used for two point, non parametric linkage analysis (NPL), maximum Lod score and transmission/ disequilibrium test (TDT) in this study Results The results of TDT indicated relatively small P values at D1S1678, D3S1744, D4S1604, D13S800, D7S483 and D8S255 (0 01< P <0 05) No significant linkages was found at any locus by Lod score and NPL analysis ( Lod ≤-1, P ≥0 05). Conclusions TDT is considered as a sensitive test for detecting linkage disequilibrium Significant linkage was found at 6 of the 13 loci typed in Chinese nuclear families with hypertension by using TDT, but no evidence suggested linkage of any locus to EH by NPL and Lod score. It is worthwhile to pay attention to chromosomal regions near the loci with small P values.