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血管紧张素原基因的M235T变异与孕期自我报告的高血压发病有关:前瞻性欧洲癌症与营养前瞻性调查(Prospect-EPIC)队列研究

The M235T variant of the angiotensinogen gene is related to development of self-reported hypertension during pregnancy: the Prospect-EPIC cohort study.

作者信息

Zafarmand Mohammad Hadi, Franx Arie, Sabour Siamak, van der Schouw Yvonne T, Grobbee Diederick E, de Leeuw Peter W, Bots Michiel L

机构信息

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Str 6.131, 3584 CX, Utrecht, The Netherlands.

出版信息

Hypertens Res. 2008 Jul;31(7):1299-305. doi: 10.1291/hypres.31.1299.

Abstract

Angiotensinogen gene (AGT) M235T polymorphism is associated with an increased risk of hypertension. It is unknown whether this mutation also leads to an increased risk of development of high blood pressure (BP) in pregnancy. The aim of this study was to investigate the association of this polymorphism with elevated blood pressure during pregnancy in a population of healthy Dutch women. We studied a randomly selected sample of 1,736 middle-aged women who participated in a prospective cohort study of 17,357 Dutch women. After excluding those who had never been pregnant or those with missing data, 429 women with and 921 women without a history of elevated BP during pregnancy remained for further analyses. History of hypertension in pregnancy was assessed using a questionnaire, and confirmed cases varied in severity from mild blood pressure elevation to pre-eclampsia. Individuals with the TT genotype were more likely to have had a history of elevated BP during pregnancy than those with the MM genotype (odds ratio [OR] = 1.43; 95% confidence interval [CI], 1.02-2.01; p = 0.04). In heterozygote individuals (MT) an increased risk was found, which did not reach statistical significance (OR = 1.24; 95% CI, 0.96-1.60; p = 0.11). Under both dominant and additive genetic models, the M235T polymorphism was associated with a history of elevated blood pressure during pregnancy, with ORs of 1.29 (95% CI, 1.01-1.64; p = 0.04) and 1.20 (95% CI, 1.02-1.42; p = 0.03), respectively. The findings of this study among Caucasian Dutch women, aged 49 to 70 years, demonstrated that the presence of the T allele of the M235T polymorphism in the AGT is associated with self-reported hypertensive disorders in pregnancy.

摘要

血管紧张素原基因(AGT)M235T多态性与高血压风险增加相关。尚不清楚该突变是否也会导致孕期高血压(BP)发生风险增加。本研究的目的是在一群健康的荷兰女性中调查这种多态性与孕期血压升高之间的关联。我们研究了从17357名荷兰女性参与的前瞻性队列研究中随机抽取的1736名中年女性样本。在排除从未怀孕或有缺失数据的女性后,剩余429名有孕期血压升高史的女性和921名无孕期血压升高史的女性进行进一步分析。使用问卷评估孕期高血压病史,确诊病例的严重程度从轻度血压升高到先兆子痫不等。与MM基因型个体相比,TT基因型个体孕期有血压升高史的可能性更大(优势比[OR]=1.43;95%置信区间[CI],1.02 - 2.01;p = 0.04)。在杂合子个体(MT)中发现风险增加,但未达到统计学显著性(OR = 1.24;95% CI,0.96 - 1.60;p = 0.11)。在显性和加性遗传模型下,M235T多态性均与孕期血压升高史相关,OR分别为1.29(95% CI,1.01 - 1.64;p = 0.04)和1.20(95% CI,1.02 - 1.42;p = 0.03)。本研究在49至70岁的荷兰白人女性中的结果表明,AGT中M235T多态性的T等位基因的存在与自我报告的孕期高血压疾病相关。

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