The Relationship Between ACE, AT₁R, ENOS Gene Polymor-phisms And Hypertensive Disorders Complicating Pregnancy

Hypertensive disorders complicating pregnancy (HDCP) is a pregnancy-specific disease, the incidence in foreign countries is 7% to 12% and in china is 9.4%～10.4%. The disease is seriously affecting maternal and child health, it remains a leading cause of maternal and newborn mortality. The etiology and pathogenesis of HDCP is not fully understood, the current accepted theories includ immune maladaptation theory, theory of placental ischemia, oxidative stress theory and the theory of genetic suscep-tibility and so on. However, these theories are not mutually isolated, but influence each other, which run through the theory of genetic susceptibility to various theories, and because the mother's genetic susceptibility is not determined by one gene, but by a group of genetically determined.This set of genes may be involved in all the key material genetic information changes in a variety of theories. Renin-angiotensin system (RAS) is an important system to maintain water and salt balance and cardio-vascular conditioning, angiotensinⅡ(AngⅡ) is the mainly effective material in the RAS, AngⅡis the most important vasoconstrictor substances, angiotensin con-verting enzyme (angiotensin-converting enzyme, ACE) is the rate-limiting enzyme generating AngⅡ, angiotensinⅡreceptor 1 (angiotensiveⅡreceptor 1, AT1R) is the main receptor of AngⅡto produce biological effects. The nitric oxide (NO) is the most effective vasodilator in our body known for maintaining an important role in vasomotor function, endothelial nitric oxide synthase (eNOS) is the only rate-limiting enzyme for vascular endothelial cells to produce NO. ACE, AT1R, eNOS plays an important role in regulating blood pressure and maintening of endothelial cell func-tion, and the gene plays a key role in encoding the protein yield and activity of the protein. Using molecular methods to find susceptibility genes is the hot spot in the cause of HDCP. The study of ACE, AT1R, eNOS gene polymorphism is important to reveal the cause of HDCP.ObjectiveTo investigate the relationship between maternal angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, angiotensinⅡreceptor 1 (AT1R) A1166C gene polymorphism or endothelial nitric oxide synthase (eNOS) gene G894T polymorphism and hypertensive disorders complicating pregnancy.MethodsBy Taqman-MGB technology to detect ACE gene I/D polymorphism, ATIR gene A1166C polymorphism and the eNOS gene G894T polymorphism in 89 cases of patients with hypertensive disorders complicating pregnancy (case group) and 120 uncomplicated pregnancy women (control group) who delivery at the Third Affiliated Hospital of Zhengzhou University Hospital in October 2009 to May 2010 with their blood, then analysis the genotype and allele frequency.SPSS 17.0 statistical analysis software used for statistical analysis, measurement data showed as mean±standard deviation(x±s), mean comparison between groups using independent t test, genotype and allele frequencies by counting method, usingχ2 test for Hardy-Weinberg genetic equilibrium test and the two groups of geno-types and allele frequencies compare. Using odds ratio (OR value) calculated the relative risk, test level is a=0.05. Results1 ACE gene I/D polymorphism in gene frequency does not meet the Hardy-Weinberg genetic equilibrium in case group, genotype distributions were con-sistent with the Hardy-Weinberg law of genetic equilibrium in control group.2 ACE genotype distribution between the two groups were significantly different, patient group ACE gene ID genotype (31.46%) was significantly lower than the con-trol group (47.50%)(P<0.05), DD genotype (41.57%) was significantly higher (27.50%)(P<0.05); case group D allele frequency (57.30%) and control group (51.25%) showed no significant difference(P>0.05).3 AT1R gene AA genotype in case group (83.15%) was significantly lower than the control group (92.50%)(P<0.05), only one case of CC genotype was detected in the control group, so the AC and CC genotypes genotypes merger analysis, the com-bined case and control groups AC+CC genotype frequency was significantly, AC genotype frequency in case group significantly higher than the AC+CC genotype frequency in control group(P<0.05). Carrying AA genotype relative to the AC geno-type OR was 2.813; cases of group C allele frequency (8.43%) and control group (4.17%) showed no significant difference (P>0.05).4 eNOS genotype and allele frequencies showed no significantly different in case group and control group(P>0.05). GG genotype in case group was 80.90% and in control group was 78.33%; GT genotype frequencies in case group was 17.98% and in control group was 20.83%; TT genotype frequency of 1.12% in the case group and control group was 0.83%. T allele frequency in case group was10.11% and in the control group was 11.25%.5 Joint analysis of genotype was not significant.Conclusions1 Maternal ACE gene I/D polymorphism may be associated with hypertensive disorders complicating pregnancy, DD genotype may increase susceptibility to hy-pertensive disorders complicating pregnancy. 2 Maternal AT1R gene Al 166C polymorphism may be associated with hyperten-sive disorders complicating pregnancy, AC and CC genotypes may increase suscepti-bility to hypertensive disorders complicating pregnancy.3 The study did not find that maternal eNOS gene G894T polymorphism is asso-ciated with hypertensive disorders complicating pregnancy.