血管紧张素转换酶基因插入/缺失多态性与早发型子痫前期的相关性
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摘要
目的:检测血管紧张素转换酶(angiotensin-converting enzyme,ACE)基因插入(insertion,I)/缺失(deletion,D)多态性,探讨ACE基因I/D多态性与早发型子痫前期的关系;探讨ACE基因I/D多态性与早发型子痫前期病情的关系。
方法:1.研究对象:2006年9月-2007月9月在江西省妇幼保健院住院治疗和分娩的孕产妇,子痫前期120例(包括早发型子痫前期60例和晚发型子痫前期60例)和正常孕妇60例。
2.研究方法:采用聚合酶链反应(polymerase chain reaction,PCR)技术检测ACE基因I/D多态性,计算基因型频率和等位基因频率,用统计学方法分析ACE基因基因型和等位基因与早发型子痫前期及其病情的关系。
结果:1.120例子痫前期和60例正常孕妇ACE基因型分布符合Hardy-Weinberg平衡定律。
2.早发型子痫前期组与晚发型子痫前期组比较,两组间ACE基因型分布差异有统计学意义(P＜0.05),等位基因频率差异有显著统计学意义(P＜0.01);早发型子痫前期组与正常孕妇组ACE基因型分布比较,差异有统计学意义(P＜0.05),等位基因频率差异有显著统计学意义(P＜0.01);晚发型子痫前期组与正常孕妇组比较,ACE基因型分布和等位基因频率均无统计学差异(P＞0.05);
3.子痫前期肾功能损害组与子痫前期无肾功能损害组比较,两组间ACE基因型分布差异有统计学意义(P＜0.05),而等位基因频率差异无统计学意义(P＞0.05);子痫前期ACE基因型组间血肌酐值有差异,DD基因型血肌酐明显升高(P＜0.05)。
4.早发型子痫前期肾功能损害发生率显著高于晚发型子痫前期(P＜0.01)。
结论:1.ACE基因I/D多态性与早发型子痫前期相关,DD基因型易患早发型子痫前期;
2.ACE基因I/D多态性与子痫前期肾功能损害相关,DD基因型可能是子痫前期肾功能损害的危险因素;
3.ACE基因DD型可能通过影响肾脏功能参与早发型子痫前期的发生和发展;
Objective: Examine the Insertion/Deletion polymorphism of angiotensin converting enzyme(ACE) gene, so that to detect the correlation between the Insertion/Deletion polymorphism of ACE gene and early onset preeclampsia and to investigate the relationship between the Insertion/Deletion polymorphism of ACE gene and the severity of early onset preeclampsia.
Methods: 1. Study object: One hundred and twenty preeclamptic patients including 60 early onset cases and 60 later onset cases and 60 normal pregnant women were recruited from Women and Children Health Hospital of Jiangxi Province during September 2006 and September 2007.
2. Method: The Insertion/Deletion polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). The frequencies of ACE genotypes and alleles were counted and compared between preeclampsia and control group respectively. Statistical analysis was conducted to determine the correlation between the gene polymorphism and early onset preeclampsia.
Results: 1. The distribution of ACE genotypes in preeclampsia group and normal pregnant group were according with Hardy-Weinberg equilibrium law.
2. The distribution of ACE genotype between early onset preeclampsia group and late onset preeclampsia group was different (P<0.05)and the frequency of allele was significantly different(P<0.01). The distribution of ACE genotype between early onset preeclampsia group and normal pregnant group was different (P<0.05)and the frequency of allele was significantly different (P<0.01) . There were no differences in the distribution of ACE genotype and the frequency of allele between late onset preeclampsia group and normal pregnant group(P>0.05).
3. The difference in the distribution of ACE genotype between preeclampsia with renal dysfunction group and preeclampsia without renal dysfunction group was significantly(P<0.05), but there was no significant difference in the frequency of allele between two groups(P>0.05). The plasma creatinine in ACE genotypes' group was different, the plasma creatinine of DD genotype group was the highest in three genotypes(P<0.05).
4. The incidence of renal dysfunction in early onset preeclampsia was significantly higher than late onset preeclampsia(P<0.01).
Conclusions: 1. The insertion/deletion polymorphism of ACE gene associated with early onset preeclampsia. The DD genotype was susceptible to early onset preeclampsia.
2. The insertion/deletion polymorphism of ACE gene associated with the renal dysfunction of preeclamptic patients. The DD genotype was a high risk predict for preeclampsia complicated with renal dysfunction.
3. The DD genotype maybe contributes to the occurrence and development of early onset preeclampsia through influencing renal function.
方法:1.研究对象:2006年9月-2007月9月在江西省妇幼保健院住院治疗和分娩的孕产妇,子痫前期120例(包括早发型子痫前期60例和晚发型子痫前期60例)和正常孕妇60例。
2.研究方法:采用聚合酶链反应(polymerase chain reaction,PCR)技术检测ACE基因I/D多态性,计算基因型频率和等位基因频率,用统计学方法分析ACE基因基因型和等位基因与早发型子痫前期及其病情的关系。
结果:1.120例子痫前期和60例正常孕妇ACE基因型分布符合Hardy-Weinberg平衡定律。
2.早发型子痫前期组与晚发型子痫前期组比较,两组间ACE基因型分布差异有统计学意义(P＜0.05),等位基因频率差异有显著统计学意义(P＜0.01);早发型子痫前期组与正常孕妇组ACE基因型分布比较,差异有统计学意义(P＜0.05),等位基因频率差异有显著统计学意义(P＜0.01);晚发型子痫前期组与正常孕妇组比较,ACE基因型分布和等位基因频率均无统计学差异(P＞0.05);
3.子痫前期肾功能损害组与子痫前期无肾功能损害组比较,两组间ACE基因型分布差异有统计学意义(P＜0.05),而等位基因频率差异无统计学意义(P＞0.05);子痫前期ACE基因型组间血肌酐值有差异,DD基因型血肌酐明显升高(P＜0.05)。
4.早发型子痫前期肾功能损害发生率显著高于晚发型子痫前期(P＜0.01)。
结论:1.ACE基因I/D多态性与早发型子痫前期相关,DD基因型易患早发型子痫前期;
2.ACE基因I/D多态性与子痫前期肾功能损害相关,DD基因型可能是子痫前期肾功能损害的危险因素;
3.ACE基因DD型可能通过影响肾脏功能参与早发型子痫前期的发生和发展;
Objective: Examine the Insertion/Deletion polymorphism of angiotensin converting enzyme(ACE) gene, so that to detect the correlation between the Insertion/Deletion polymorphism of ACE gene and early onset preeclampsia and to investigate the relationship between the Insertion/Deletion polymorphism of ACE gene and the severity of early onset preeclampsia.
Methods: 1. Study object: One hundred and twenty preeclamptic patients including 60 early onset cases and 60 later onset cases and 60 normal pregnant women were recruited from Women and Children Health Hospital of Jiangxi Province during September 2006 and September 2007.
2. Method: The Insertion/Deletion polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). The frequencies of ACE genotypes and alleles were counted and compared between preeclampsia and control group respectively. Statistical analysis was conducted to determine the correlation between the gene polymorphism and early onset preeclampsia.
Results: 1. The distribution of ACE genotypes in preeclampsia group and normal pregnant group were according with Hardy-Weinberg equilibrium law.
2. The distribution of ACE genotype between early onset preeclampsia group and late onset preeclampsia group was different (P<0.05)and the frequency of allele was significantly different(P<0.01). The distribution of ACE genotype between early onset preeclampsia group and normal pregnant group was different (P<0.05)and the frequency of allele was significantly different (P<0.01) . There were no differences in the distribution of ACE genotype and the frequency of allele between late onset preeclampsia group and normal pregnant group(P>0.05).
3. The difference in the distribution of ACE genotype between preeclampsia with renal dysfunction group and preeclampsia without renal dysfunction group was significantly(P<0.05), but there was no significant difference in the frequency of allele between two groups(P>0.05). The plasma creatinine in ACE genotypes' group was different, the plasma creatinine of DD genotype group was the highest in three genotypes(P<0.05).
4. The incidence of renal dysfunction in early onset preeclampsia was significantly higher than late onset preeclampsia(P<0.01).
Conclusions: 1. The insertion/deletion polymorphism of ACE gene associated with early onset preeclampsia. The DD genotype was susceptible to early onset preeclampsia.
2. The insertion/deletion polymorphism of ACE gene associated with the renal dysfunction of preeclamptic patients. The DD genotype was a high risk predict for preeclampsia complicated with renal dysfunction.
3. The DD genotype maybe contributes to the occurrence and development of early onset preeclampsia through influencing renal function.
引文
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[3]Poston L.Endothelial dysfunction in preelampsia.Pharmacol.Rep,2006,58:69-74
[4]Schiessl B.Inflammatory response in preeclampsia.Mol Aspects Med,2007,28(2):210-219
[5]Mandang S,Manuelpillai U,Wallace EM.Oxidative stress increases placental and endothelial cell activin-A secretion.J Endocrinol,2007,192(3):485-493
[6]Salonen RH,Lichtenstein P.Genetic effects on the liability of developing pre-eclampsia and gestational hypertension.American Journal of Medical Genet,2000,91:256-260
[7]Mello G,Parretti E,Gensini F,et al.Maternal-fetal flow,negative events,and preeclampsia:role of ACE I/D polymorphism.Hypertension,2003,41(4):932-937
[8]Pell JP,Smith GC,Walsh D.Pregnancy complications and subsequent maternal cerebrovascular events:a retrospective cohort study of 119,668 births.Am J Epidemiol,2004,159:336-342
[9]Nielsen AH,Schauser KH,Poulsen K.Current topic:the utero-placental renin-angiotensin system.Placenta,2000,21:468-477
[10]乐杰主编《妇产科学》第6版.北京:人民卫生出版社,2004.99-100
[11]丰有吉主编《妇产科学》(7年制教材).北京:人民卫生出版社.
[12]Walsh PS,Metzger DA,Higuchi R.Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material[J].Bio-techniques,1991,10(4):506-513
[13]Hubert C,Houot AM,Corvol P,et al.Structure of the angiotensin I-converting enzyme(ACE)gene:Two alternate promoters correspond to evolutionary steps of a duplicated gene.J Biol Chem,1991,266(8):1537-1544
[14]Rigat B,Hubert C,Corvol P,et al.PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene(DCP1).Nucleic Acids Res,1992,20(9):1433-1438
[15]Chunbiao Li,Rais Ansari,Ziming Yu,et al.Definitive Molecular Evidence of Renin-Angiotensin System in Human Uterine Decidual Cells.Hypertension,2000,36:159-164
[16]Dinesh M.Shah.Preeclampsia:new insights.Nephrology and Hypertension,2007,16:213-220
[17]Phyllis,August,France B.Role of renin-angiotensin system in blood pressure regulation in pregnancy.Lancet,1995,345:896-897
[18]王美.血管紧张素Ⅱ对滋养细胞侵袭力的影响.第三军医大学学报,2006,28(11):1201-1203
[19]Naden R,Rosenfeld C.Effect of angiotensin Ⅱ on uterine and systemic vasculature in pregnant sheep.J Clin Invest,1981,68:468-474
[20]Herse F,Dechend R,Harsem NK,et al.Dys-regulation of the circulating and tissue-based renin-angiotensin system in preeclampsia.Hypertension,2007,49(3):604-611
[21]F.A.Sayed-Yabatabaei,B.A.Oostra,A.Isaacs,C.M,et al.ACE Polymorphisms.Circ.Res,2006,98:1123-1133
[22]Gao Chun,Gu Guo-hao,Xia Zheng.Genetic polyrnorphism of angiotensin-converting enzyme gene insertion /deletion in Chinese Han population.Chinese Journal of Clinical Rehabilitation,2006,44(10):188-190
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