Borecki I B, Province M A, Ludwig E H, Ellison R C, Folsom A R, Heiss G, Lalouel J M, Higgins M, Rao D C
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ann Epidemiol. 1997 Jan;7(1):13-21. doi: 10.1016/s1047-2797(97)00155-5.
In studies conducted in several different populations, the M235T substitution in the angiotensinogen (AGT) locus has been associated with hypertension.
A case-control study was initiated in an attempt to replicate this finding. Persons with hypertension, age- and sex-matched normotensive controls, and randomly sampled individuals were probands from the Family Heart Study of the National Heart, Lung, and Blood Institute. Subjects were recruited from the Atherosclerosis Risk in Communities study (ARIC) in North Carolina and Minneapolis, MN, and from the Framingham Heart Study in Massachusetts. Genotypes were determined for the M235T substitution in the AGT locus and for the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) locus. Simple association tests as well as logistic regression analyses were performed.
The association of AGT-T235 with hypertension was replicated in the Framingham sample (odds ratio, 1.60; 95% confidence interval, 1.11-2.30), but not in the ARIC white or black subjects. However, logistic regression analysis suggested a significant association of AGT with hypertension in both the ARIC white and Framingham samples when the effects of body mass index, triglycerides, and the presence of significant coronary heart disease were controlled. These analyses further suggested that, in the ARIC data, the relationship with the AGT locus is stronger in women than men and that there may be interaction (epistasis) between homozygotes for T235 and ACE-DD in the Framingham data. While the small sample size precluded logistic regression analysis, the frequency of the T235 allele in the black random sample was much higher than in the comparable white sample.
These results are compatible with the presence of a genetic risk factor for hypertension in or near the angiotensinogen locus.
在针对多个不同人群开展的研究中，血管紧张素原（AGT）基因座中的M235T替换与高血压相关。
启动了一项病例对照研究以试图重现这一发现。患有高血压的人、年龄和性别匹配的血压正常对照者以及随机抽样的个体是美国国立心肺血液研究所家庭心脏研究的先证者。受试者从北卡罗来纳州和明尼苏达州明尼阿波利斯的社区动脉粥样硬化风险研究（ARIC）以及马萨诸塞州的弗雷明汉心脏研究中招募。确定了AGT基因座中M235T替换以及血管紧张素转换酶（ACE）基因座中插入/缺失多态性的基因型。进行了简单关联测试以及逻辑回归分析。
AGT - T235与高血压的关联在弗雷明汉样本中得到重现（优势比，1.60；95%置信区间，1.11 - 2.30），但在ARIC的白人或黑人受试者中未得到重现。然而，逻辑回归分析表明，当控制体重指数、甘油三酯以及显著冠心病的存在等因素的影响时，AGT与ARIC白人样本和弗雷明汉样本中的高血压均存在显著关联。这些分析进一步表明，在ARIC数据中，AGT基因座与高血压的关系在女性中比男性更强，并且在弗雷明汉数据中，T235纯合子与ACE - DD之间可能存在相互作用（上位性）。虽然样本量小使得无法进行逻辑回归分析，但黑人随机样本中T235等位基因的频率远高于可比的白人样本。
这些结果与血管紧张素原基因座内或其附近存在高血压遗传风险因素相一致。
