血管紧张素转换酶2与血管紧张素转换酶基因多态性相互作用增加女性高血压发病易感性

Polymorphism Interaction Between Angiotensin-Convertion Enzyme 2 Gene and Angiotensin-Convertion Enzyme Gene on the Risk of Essential Hypertension in Women

目的:探讨血管紧张素转换酶2(ACE2)和ACE基因多态性是否相互作用增加高血压发病易感性。方法:挑选ACE2基因的5个标签单核苷酸多态及ACE基因I/D多态性,采用标准的多聚酶链反应—限制性片段长度多态性技术进行基因分型,抽取部分测序验证。通过2组病例—对照研究[信阳:高血压病例973例(男性病例357例,女性病例616例)和对照969例(男性对照者355例,女性对照者614例);日照:病例286例(男性病例101例,女性病例185例)和对照316例(男性对照者126例,女性对照者190例)验证ACE2和ACE基因多态性与高血压的相关性。结果:ACE2基因rs2106809TT基因型和T等位基因分布频率在女性病例中显著高于女性对照者(OR:1.21,95%CI:1.09～1.34,P<0.001),差异有统计学意义;男性无统计学意义。未发现其它基因多态在两者间有统计学意义。Lo-gistic回归分析调整年龄、血脂、血糖等危险因素后,女性病例T等位基因携带者与女性对照者比较高血压易感性增加1.6倍(OR:1.59,95%CI:1.13～2.06,P<0.001),差异有统计学意义。女性病例ACEDD基因型+ACE2 rs2106809TT/TC基因型分布频率显著高于女性对照者(11.7%vs6.0%,P<0.001),差异有统计学意义。Logistic回归分析证实女性病例中ACE基因I/D与ACE2 rs2106809有交互作用(OR:1.25,95%CI:1.18～1.34,P<0.001),同时携带ACEDD中的ACE2 rs2106809TT/TC基因型者高血压危险增加(OR:2.75,95%CI:1.58～4.77,P<0.001),与对照者比较差异有统计学意义。上述结果在第二组病例对照研究中得到验证。结论:ACE2T等位基因是女性高血压的独立危险因素,ACEDD基因型增加这种危险。

Objective ：To investigate the interaction of polymorphisms between angiotensin-convertion enzyme （ACE）2 gene and ACE gene as the risk factor of essential hypertension. Methods：Five tagging single nucleotide polymorphisms of ACE2 and the I/D polymorphism in intron 16 of ACE gene were selected according to HapMap data and previous studies. Standard PCR restriction fragment length polymorphism（RFLP） analysis was used to determine genotypes, and subsequently confirmed by randomly selected bidirectional sequencing. Two case control studies were conducted,first in 973 patients and 969 controls recruited in Xinyang,and then in 286 patients and 316 controls recruited in Rizhao. Results：The frequency of T allele of ACE2 rs2106809 locus was significantly higher in female hypertension patients than in female controls （crude OR：I. 21,95 % CI：I. 09 - 1.34, P 〈 0. 001 ） , but this difference was not found in men. No differences were found in other polymorphisms of ACE2 and ACE I/D between patients and controls. After adjustment of age, body mass index and other conventional risk factors, the T allele conferred 1.6-fold risk of hypertension in women （ OR ： 1.59,95 % CI ： 1.13 - 2. 06, P 〈0. 001 ）. Female carriers with ACE2 T allele and ACE DD genotype were significantly more common in hypertension patients than in controls（ 11.7% vs 6.0% ,P 〈 0. 001 ）. ACE2 rs2106809 interacted with ACE genotypes to increase the risk of hypertension in women（ OR： 1.25,95% CI： 1.18 - 1.34,P =0. 001 ）. In female patients with ACE DD genotype,ACE2 T allele conferred 2. 75-fold risk for hypertension（95 % CI： 1.58 - 4. 77, P 〈 0,001 ）. These results were reproduced and confirmed in the second ease control study. Conclusion： ACE2 T allele confered high risk of hypertension in women, and ACE DD genotype increased this risk.