Linkage of angiotensinogen gene polymorphisms with hypertension in a sibling study of Hong Kong Chinese.
Linkage of angiotensinogen gene polymorphisms with hypertension in a sibling study of Hong Kong Chinese.
复制标题
香港华人同胞研究中血管紧张素原基因多态性与高血压的关联。
DOI：
10.1097/hjh.0b013e3283384b07
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发表时间：
2010-06
影响因子：
4.9
通讯作者：
Tomlinson, Brian
中科院分区：
文献类型：
--
作者：
Fang, Yu-Jing;Deng, Han-Bing;Thomas, G. Neil;Tzang, Chi H.;Li, Cai-Xia;Xu, Zong-Li;Yang, Mengsu;Tomlinson, Brian
血管紧张素原基因与白种人的原发性高血压有关，但在亚洲人群中的关系不太一致。本研究旨在探讨血管紧张素原基因M235 T、T174 M和G-217 A多态性与中国同胞高血压的遗传关联。我们研究了126个有高血压先证者的家庭成员，包括434个兄弟姐妹，其中178个是高血压。记录父母高血压史。M235 T，T174 M和G-217 A多态性进行了检查，使用微阵列方法，测序验证。应用传递不平衡检验确定遗传多态性位点是否与高血压相关。使用TRANSMIT程序对组合的多态性进行单体型分析。应用受影响家系成员法进行连锁分析。M235 T多态性与高血压有显著的过度传递（χ2=4.41，p=0.036），而T174 M和G-217 A多态性与高血压无显著的过度传递（χ2=4.41，p=0.036）。单倍型分析显示与成对标记（T174和T235）的单倍型显著相关，χ2值为8.131，p=0.004（总体检验χ2=9.131，p=0.028）。M235 T基因多态性与高血压存在连锁关系（T=-2.25，P =0.019），M235 T和T174 M基因多态性与中心性肥胖相关的高血压存在连锁倾向（P=0.0087和P=0.01）。M235 T和T174 M变异，尤其是T235等位基因，导致这些中国受试者高血压风险增加。
The angiotensinogen gene has been linked with human essential hypertension in Caucasians but the relationship in Asian populations has been less consistent. This study aimed to examine genetic associations between hypertension and the M235T, T174M, and G-217A polymorphisms of the angiotensinogen gene in Chinese siblings. We studied members of 126 families with a hypertensive proband, including 434 siblings, of which 178 were hypertensive. Parental history of hypertension was recorded. The M235T, T174M, and G-217A polymorphisms were examined using a microarray method, validated by sequencing. The transmission disequilibrium test was applied to identify whether the genetic polymorphism loci were related to hypertension. Haplotype analysis of the combined polymorphisms was applied using the TRANSMIT program. Linkage study was conducted by applying the affected pedigree member method. A significant over-transmission was observed for the T235 allele at the M235T polymorphism and hypertension (χ2=4.41, p=0.036), but not for the T174M and G-217A polymorphisms. The haplotype analysis showed a significant association with the haplotypes of paired markers (T174 and T235) with χ2 value of 8.131, p=0.004 (global test χ2=9.131, p=0.028). Linkage between M235T and hypertension was detected (T=-2.25, P=0.019), and a tendency for linkage with central obesity-related hypertension was found for the M235T and T174M polymorphisms (P=0.0087 and P=0.01). The M235T and T174M variants, especially the T235 allele, contribute to an increased risk of hypertension in these Chinese subjects.