Ishikawa K, Baba S, Katsuya T, Iwai N, Asai T, Fukuda M, Takiuchi S, Fu Y, Mannami T, Ogata J, Higaki J, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Osaka, Japan.
Hypertension. 2001 Feb;37(2):281-5. doi: 10.1161/01.hyp.37.2.281.
A common variant at codon 235 of the angiotensinogen gene with methionine to threonine amino acid substitution (AGT M235T) has been reported as a genetic risk for essential hypertension. However, the frequency of AGT T235 was heterogeneous among races, and a positive association between AGT M235T and hypertension was not settled. To examine the association in a general population of Japanese (n=4013), we introduced the TaqMan polymerase chain reaction method and examined the relation between hypertension and T+31C polymorphism, which was in absolute linkage disequilibrium with AGT M235T. The C+31 allele of AGT was significantly associated with the positive family history of hypertension (FH) but not with the presence of hypertension or blood pressure. The subjects with CC tended to have hypertensive relatives, especially a hypertensive father or siblings, and its statistical significance was stronger in men. Adjustment of confounding factor did not alter the results of simple association study, suggesting that this positive association with FH is independent and significant. Our findings revealed that the TaqMan polymerase chain reaction method is a powerful tool for genetic association study with a large number of subjects and that AGT T+31C is significantly associated with paternal FH.
血管紧张素原基因第235密码子处的一个常见变异（甲硫氨酸替换为苏氨酸，AGT M235T）已被报道为原发性高血压的遗传风险因素。然而，AGT T235的频率在不同种族间存在差异，并且AGT M235T与高血压之间的正相关关系尚未确定。为了在日本普通人群（n = 4013）中研究这种相关性，我们采用了TaqMan聚合酶链反应方法，并研究了高血压与T + 31C多态性之间的关系，该多态性与AGT M235T处于完全连锁不平衡状态。AGT的C + 31等位基因与高血压家族史（FH）呈显著相关，但与高血压的存在或血压水平无关。携带CC基因型的受试者往往有高血压亲属，尤其是父亲或兄弟姐妹患有高血压，且在男性中这种统计学意义更强。混杂因素的校正并未改变单因素关联研究的结果，这表明与FH的这种正相关是独立且显著的。我们的研究结果表明，TaqMan聚合酶链反应方法是进行大量受试者基因关联研究的有力工具，并且AGT T + 31C与父亲的FH显著相关。
