Anderson J L, Carlquist J F, King G J, Morrison L, Thomson M J, Ludwig E H, Muhlestein J B, Bair T L, Ward R H
Division of Cardiology, University of Utah, LDS Hospital, Salt Lake City 84143, USA.
J Am Coll Cardiol. 1998 Mar 15;31(4):790-6. doi: 10.1016/s0735-1097(98)00007-2.
We tested for an association between the angiotensin-converting enzyme (ACE) DD polymorphic genotype and myocardial infarction (MI) in a sample group composed exclusively of women.
The human ACE gene occurs with either an insertion (I allele) or a deletion (D allele) of a 287-base pair (bp) Alu element. Part of the variance in serum ACE levels may be accounted for by this polymorphism. Also, the DD genotype has been associated with an increased risk of MI in predominantly male populations. However, the risk in women is poorly defined.
Genomic DNA was extracted from buffy coat blood using a phenol/chloroform method. Angiotensin-converting enzyme alleles were identified using primers to bracket the insertion region in intron 16. Amplification using polymerase chain reaction allowed identification of a 490-bp (I allele) or a 190-bp (D allele) product, or both.
Allelic and genotypic frequencies in control subjects were similar to those reported in mostly male populations, and frequencies of genotypes were in the Hardy-Weinberg equilibrium. In contrast, the distribution of genotypes in patients with MI diverged from the equilibrium. Specifically, DD genotypic frequency was increased in women with (n = 141) versus without (n = 338) a previous MI (39% vs. 29%, odds ratio [OR] 1.54, 95% confidence interval 1.02 to 2.32, p < 0.04). Risk was particularly increased in women <60 years old (OR 2.04, p < 0.05). In contrast, the DD genotype did not predict angiographic coronary artery disease.
Consistent with findings in male-dominated populations, a modest association of the ACE DD genotype with MI was found in women. The basis for this association requires further study.
我们在一个仅由女性组成的样本组中检测血管紧张素转换酶（ACE）DD多态性基因型与心肌梗死（MI）之间的关联。
人类ACE基因存在287个碱基对（bp）的Alu元件插入（I等位基因）或缺失（D等位基因）。这种多态性可能是血清ACE水平部分差异的原因。此外，DD基因型在以男性为主的人群中与MI风险增加有关。然而，女性中的风险尚不明确。
采用酚/氯仿法从血沉棕黄层血液中提取基因组DNA。使用引物鉴定血管紧张素转换酶等位基因，该引物围绕第16内含子中的插入区域。通过聚合酶链反应进行扩增，可鉴定出490 bp（I等位基因）或190 bp（D等位基因）产物，或两者皆有。
对照组中的等位基因和基因型频率与大多男性人群中报告的频率相似，且基因型频率处于哈迪-温伯格平衡。相比之下，MI患者的基因型分布偏离平衡。具体而言，有过MI的女性（n = 141）与无MI的女性（n = 338）相比，DD基因型频率增加（39%对29%，优势比[OR] 1.54，95%置信区间1.02至2.32，p < 0.04）。60岁以下女性的风险尤其增加（OR 2.04，p < 0.05）。相比之下，DD基因型不能预测血管造影显示的冠状动脉疾病。
与男性占主导的人群中的发现一致，在女性中发现ACE DD基因型与MI存在适度关联。这种关联的基础需要进一步研究。
