Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Hypertens Res. 2010 May;33(5):473-7. doi: 10.1038/hr.2010.23. Epub 2010 Feb 26.
We investigated the variations in genes encoding endothelial nitric oxide synthase (NOS3), angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) in hypertensive disorders of pregnancy and the relationship between the polymorphisms and circulating nitric oxide (NO) and ACE levels in pregnant north Indian women. Frequencies of NOS3 G894T, 4b/a and T(-786) --> C, AGT T704C and ACE ins/del polymorphisms were studied in 342 subjects: 120 with preeclampsia (PE), 104 with gestational hypertension and 118 normotensive pregnant women. Variations were evaluated by polymerase chain reaction-restriction fragment length polymorphism. NO and ACE levels were determined using ELISA. There was no difference in the distribution of individual NOS3 and ACE polymorphisms in the study groups. Haplotype analysis showed a global difference in the NOS3 haplotype distribution between the PE and non-PE subjects (P=0.03). The presence of AGT 704C allele was associated with a reduced risk of developing PE (odds ratio: 0.33, 95% CI: 0.19-0.59 in recessive mode). Circulating total NO and ACE levels were similar in three groups. No relationship was found between circulating NO levels and any of the NOS3 polymorphisms, but the circulating ACE levels were higher in those with DD genotype (P<0.05). In conclusion, there was no association between individual NOS3 and the ACE gene polymorphisms and hypertensive disorders of pregnancy in north Indian women. The presence of minor alleles at all the three sites in NOS3 seemed to increase the risk of PE, and AGT 704C allele was associated with a reduced PE risk. The complexity of interaction between these genetic abnormalities requires further studies.
我们研究了妊娠高血压疾病中内皮型一氧化氮合酶（NOS3）、血管紧张素转换酶（ACE）和血管紧张素原（AGT）基因编码的变异，以及这些多态性与北印度孕妇循环一氧化氮（NO）和 ACE 水平之间的关系。在 342 名受试者中研究了 NOS3 G894T、4b/a 和 T(-786)-->C、AGT T704C 和 ACE ins/del 多态性：120 名患有子痫前期（PE），104 名患有妊娠期高血压，118 名血压正常的孕妇。通过聚合酶链反应-限制性片段长度多态性评估变异。使用 ELISA 测定 NO 和 ACE 水平。研究组中个体 NOS3 和 ACE 多态性的分布无差异。单体型分析显示，PE 和非 PE 受试者之间 NOS3 单体型分布存在全局差异（P=0.03）。AGT 704C 等位基因的存在与发生 PE 的风险降低相关（在隐性模式下，比值比：0.33，95%CI：0.19-0.59）。三组的循环总 NO 和 ACE 水平相似。在这些多态性与循环 NO 水平之间未发现任何关系，但 DD 基因型的循环 ACE 水平较高（P<0.05）。总之，在北印度妇女中，个体 NOS3 和 ACE 基因多态性与妊娠高血压疾病之间没有关联。NOS3 中所有三个位点的次要等位基因似乎增加了 PE 的风险，而 AGT 704C 等位基因与降低 PE 风险相关。这些遗传异常之间相互作用的复杂性需要进一步研究。
