Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure
Linkage and association analysis of angiotensin I-converting enzyme (ACE)-gene polymorphisms with ACE concentration and blood pressure
复制标题
DOI：
10.1086/320104
复制
发表时间：
2001-05-01
影响因子：
9.8
通讯作者：
Ward, R
中科院分区：
文献类型：
--
作者：
Zhu, XF;Bouzekri, N;Ward, R
已经花费了相当大的努力来确定血管紧张素I转换酶（ACE）基因是否赋予心血管疾病的易感性。在这项研究中，我们对来自332个家庭的1,343名中国人的ACE基因的13个多态性进行了基因分型。为了定位遗传效应，我们首先对所有标记与ACE浓度进行了连锁和关联分析。在多点方差分量分析中，该区域与ACE浓度密切相关（最大LOD评分7.5）。同样，ACE基因的大多数多态性与ACE显著相关（P <0.0013）。两个最高度相关的多态性，ACE 4和ACE 8，分别占ACE变异的6%和19%。一个两个位点的加性模型与这些多态性的加性×加性相互作用解释了大多数与该地区相关的ACE变异。我们接下来分析了这两个多态性（ACE 4和ACE 8）与血压（BP）之间的关系。虽然没有证据表明连锁被检测到，显着的关联被发现收缩压和舒张压时，两个位点的添加剂模型开发的ACE浓度。进一步的分析表明，上位性模型提供了最好的拟合BP变化。总之，我们发现，在这个非洲人群样本中，两个多态性解释了ACE浓度的最大变化，通过相互作用与BP显着相关。我们的研究还表明，更大的统计功率可以预期与关联分析与连锁，当标记在强连锁不平衡与性状位点已被确定。此外，等位基因的相互作用可能发挥重要作用，在解剖复杂的性状，如BP。
Considerable effort has been expended to determine whether the gene for angiotensin I-converting enzyme (ACE) confers susceptibility to cardiovascular disease. In this study, we genotyped 13 polymorphisms in the ACE gene in 1,343 Nigerians from 332 families. To localize the genetic effect, we first performed linkage and association analysis of all the markers with ACE concentration. In multipoint variance-component analysis, this region was strongly linked to ACE concentration (maximum LOD score 7.5). Likewise, most of the polymorphisms in the ACE gene were significantly associated with ACE (P < .0013). The two most highly associated polymorphisms, ACE4 and ACE8, accounted for 6% and 19% of the variance in ACE, respectively. A two-locus additive model with an additive x additive interaction of these polymorphisms explained most of the ACE variation associated with this region. We next analyzed the relationship between these two polymorphisms (ACE4 and ACE8) and blood pressure (BP). Although no evidence of linkage was detected, significant association was found for both systolic and diastolic BP when a two-locus additive model developed for ACE concentration was used. Further analyses demonstrated that an epistasis model provided the best fit to the BP variation. In conclusion, we found that the two polymorphisms explaining the greatest variation in ACE concentration are significantly associated with BP, through interaction, in this African population sample. Our study also demonstrates that greater statistical power can be anticipated with association analysis versus linkage, when markers in strong linkage disequilibrium with a trait locus have been identified. Furthermore, allelic interaction may play an important role in the dissection of complex traits such as BP.