外周血ACE基因I/D、AGT基因M235T多态性与妊娠期高血压疾病的关系

Relationship between peripheral blood ACE gene I/D,AGT gene M235T polymorphism and hypertensive disorder complicating pregnancy

目的探讨外周血血管紧张素转换酶(ACE)基因I/D、血管紧张素原(AGT)基因M235T多态性与妊娠期高血压疾病(HDCP)的关系。方法选择HDCP患者200例(观察组)、健康孕妇200例(对照组),采集外周静脉血,SNaP shot基因分型技术分析ACE基因I/D、AGT基因M235T多态性,采用ELISA法检测血清ACE、AGT,比较两组外周血ACE基因I/D、AGT基因M235T基因型分布和等位基因频率以及不同基因型者血清ACE、AGT水平。收集HDCP患者临床资料,包括孕前体质量指数(BMI)、被动吸烟例数、高血压家族史、收缩压、舒张压、孕次、产次、TC、TG、肌酐(Cr)等。比较两组上述临床资料,将有统计学差异的临床资料以及外周血ACE基因I/D、AGT基因M235T多态性纳入多因素Logistic回归模型,分析影响HDCP发病的危险因素。结果两组外周血ACE基因I/D、AGT基因M235T多态性分布均符合Hardy-Weinberg遗传平衡定律,具有群体代表性。两组外周血ACE基因I/D、AGT基因M235T基因型分布和等位基因频率比较差异均有统计学意义(P均<0.05)。HDCP患者外周血ACE基因I/D DD基因型者血清ACE、AGT水平高于DI、Ⅱ基因型者,外周血AGT基因M235T TT基因型者血清ACE、AGT水平高于MM、MT基因型者(P均<0.05)。单因素分析显示,观察组孕前BMI、被动吸烟例数、有高血压家族史例数、收缩压、舒张压、产次、Cr均高于对照组(P均<0.05),而两组孕次、TC、TG比较差异均无统计学意义(P均>0.05)。多因素Logistic回归分析显示,孕前BMI、被动吸烟、产次、ACE基因I/D多态性、AGT基因M235T多态性是HDCP发病的危险因素(P均<0.01)。外周血ACE基因I/D多态性中携带DD基因型孕妇罹患HDCP的风险是携带Ⅱ基因型孕妇的1.324倍,外周血AGT基因M235T多态性中携带TT基因型孕妇罹患HDCP的风险是携带MM基因型孕妇的1.905倍。结论外周血ACE基因I/D、AGT基因M235T多态性与HDCP发病有关,携带ACE基因I/D DD基因型、AGT基因M235T TT基因型孕妇HDCP的发病风险更高。

Objective To investigate the relationship between peripheral blood angiotensin converting enzyme(ACE)gene I/D,angiotensinogen(AGT) gene M235T polymorphism and hypertensive disorder complicating pregnancy(HDCP).Methods Totally 200 HDCP patients(observation group) and 200 healthy pregnant women(control group) were selected. Peripheral venous blood samples were collected. Na Pshot genotyping technique was used to analyze ACE gene I/D and AGT gene M235T polymorphism. Serum ACE and AGT were detected by ELISA. Genotype distribution,allele frequency and serum ACE and AGT levels of different genotypes were compared between the two groups. The clinical data of HDCP patients were collected,including pre-pregnancy body mass index(BMI),number of passive smoking cases,family history of hypertension,systolic blood pressure,diastolic blood pressure,parity,TC,TG,creatinine(Cr),etc. The above clinical data of the two groups were compared,and the statistically significant differences as well as the polymorphism of ACE gene I/D and AGT gene M235T in peripheral blood were incorporated into the multivariate Logistic regression model to analyze the risk factors affecting the incidence of HDCP. Results The distribution of ACE gene I/D and AGT gene M235T polymorphism in the peripheral blood of the two groups was in accordance with Hardy Weinberg’ s law of genetic balance,which was representative of the population. The differences of ACE gene I/D,AGT gene M235T genotype distribution and allele frequency between the two groups were statistically significant(all P < 0. 05). The serum levels of ACE and AGT in HDCP patients with genotype I/D DD of ACE gene were higher than those with genotype DI and Ⅱ,and those with M235T TT genotype of AGT gene were higher than those with genotypes MM and MT(all P < 0. 05). Univariate analysis showed that the pre-pregnancy BMI,the number of cases of passive smoking,the number of cases with family history of hypertension,systolic blood pressure,diastolic blood pressure,parity and Cr in the observation group were higher than those in the control group(all P < 0. 05),while no significant difference was found in the pregnancy times,TC or TG between the two groups(all P > 0. 05). Multivariate Logistic regression analysis showed that pre-pregnancy BMI,passive smoking,parity,ACE gene I/D polymorphism and AGT gene M235T polymorphism were the risk factors of HDCP(all P < 0. 01). In ACE gene I/D polymorphism of the peripheral blood,the risk of HDCP in pregnant women carrying genotype DD was 1. 324 times that of genotype Ⅱ,and in AGT gene M235T polymorphism of the peripheral blood,the risk of HDCP in pregnant women carrying TT genotype was 1. 905 times that of MM genotype. Conclusion The I/D of ACE gene and M235T polymorphism of AGT gene in the peripheral blood are associated with HDCP,and the risk of HDCP is higher in pregnant women with genotypes DD and TT.