血管紧张素原基因M235T位点多态性与重度子痫前期的关系
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摘要
目的探讨血管紧张素原(AGT)基因M235T位点多态性与重度子痫前期的关系。方法选择择期行剖宫产的重度子痫前期孕妇133例(观察组)、无指征剖宫产的正常孕妇93例(对照组),术日清晨采集无宫缩状态下外周静脉血3 mL,采用聚合酶链反应-限制性片段长度多态性技术检测AGT基因M235T位点基因型和等位基因分布。结果两组AGT基因M235T位点基因型和等位基因分布比较差异均有统计学意义(χ~2分别为6.219、5.461,P均<0.05)。两组在校正高血压史这一混杂因素后,MT基因型者罹患重度子痫前期的危险性是MM基因型者的2.284倍(校正OR=2.284,95%CI:1.169～4.461,P<0.05);TT基因型者罹患重度子痫前期的危险性是MM基因型者的3.910倍(校正OR=3.910,95%CI:1.532～9.982,P<0.01)。两组MM、MT、TT基因型理论值与实际值比较P均>0.05,符合Hardy-Weinberg遗传平衡定律。结论 AGT基因M235T位点多态性与重度子痫前期的发病有关,尤其是TT基因型。
Objective To explore the relationship between angiotensinogen(AGT) M235 T gene polymorphism and severe preeclampsia. Methods We selected 133 pregnant women with severe preeclampsia(observation group) who would undergo elective cesarean section and 93 normal pregnant women undergoing cesarean section(control group), and collected peripheral venous blood(3 mL) on the morning of operation day without uterine contraction. The genotype and allele distribution of M235 T locus of AGT gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results There were significant differences in genotype and allele distribution of M235 T locus of AGT gene between the two groups(χ~2=6.219, 5.461, respectively; both P<0.05). The risk of severe preeclampsia in patients with MT genotype was 2.284 times higher than that of patients with MM genotype(corrected OR=2.284, 95%CI: 1.169-4.461, P<0.05), and the risk of TT genotype was 3.910 times higher than that of MM genotype(corrected OR=3.910, 95% CI: 1.532-9.982, P<0.01). Comparisons of theoretical and actual values of MM, MT and TT genotypes between the two groups were all more than 0.05, which was in accordance with Hardy-Weinberg equilibrium law. Conclusion The M235 T polymorphism of AGT gene is associated with the onset of severe preeclampsia, especially TT genotype.
Objective To explore the relationship between angiotensinogen(AGT) M235 T gene polymorphism and severe preeclampsia. Methods We selected 133 pregnant women with severe preeclampsia(observation group) who would undergo elective cesarean section and 93 normal pregnant women undergoing cesarean section(control group), and collected peripheral venous blood(3 mL) on the morning of operation day without uterine contraction. The genotype and allele distribution of M235 T locus of AGT gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results There were significant differences in genotype and allele distribution of M235 T locus of AGT gene between the two groups(χ~2=6.219, 5.461, respectively; both P<0.05). The risk of severe preeclampsia in patients with MT genotype was 2.284 times higher than that of patients with MM genotype(corrected OR=2.284, 95%CI: 1.169-4.461, P<0.05), and the risk of TT genotype was 3.910 times higher than that of MM genotype(corrected OR=3.910, 95% CI: 1.532-9.982, P<0.01). Comparisons of theoretical and actual values of MM, MT and TT genotypes between the two groups were all more than 0.05, which was in accordance with Hardy-Weinberg equilibrium law. Conclusion The M235 T polymorphism of AGT gene is associated with the onset of severe preeclampsia, especially TT genotype.
引文
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[9] 朱旭明,郁昊达,孙伟峰,等.血管紧张素原基因T174M多态性与原发性高血压相关性的Meta分析[J].实用妇产科杂志,2013,29(4):639-641.
[10] Hasimu B,Nakayama T,Mizutani Y,et al.Haplotype analysis of human renin gene and essential hypertension[J].Hypertension,2003,41(2):308-312.
[11] Sethi AA,Nordestgaard BG,Agerholm-Larsen B,et al.Angiotensinogen polymorphisms and elevated blood pressure in the general population:the Copenhagen City Heart Study[J].Hypertension,2001,37(3):875-881.
[12] Wu CH,Wang Y,Ma M,et al.Antisense oligonucleotides targeting angiotensinogen:insights from animal studies[J].Biosci Rep,2019,39(1).pii:BSR20180201.
[13] Jeunemaitre X,Inoue I,WiIliams C,et al.Haplotypes of angiotensinogen in essential hypertension[J].Am J Hum Genet,1997,60(6):1448-1460.
[14] Zitouni H,Ben Ali Gannoum M,Raguema N,et al.Contribution of angiotensinogen M235T and T174M gene variants and haplotypes to preeclampsia and its severity in (North African) Tunisians[J].J Renin Angiotensin Aldosterone Syst,2018,19(1):1470320317753924.
[15] 宋成文,谢守珍,习波,等.血管紧张素原基因多态及血管生成因子与早发型重度子痫前期的相关性研究[J].实用医学杂志,2012,28(20):3338-3340.
[16] Jenkins LD,Powers RW,Cooper M,et al.Preeclampsia risk and angiotensinogen polymorphisms M235T and AGT -217 in African American and Caucasian women[J].Reprod Sci,2008,15(7):696-701.
[2] Sibai B,Dekker G,Kupferminc M.Preeclampsia[J].Lancet,2005,365(9461):785-799.
[3] Shahvaisizadeh F,Movafagh A,Omrani MD,et al.Synergistic effects of angiotensinogen -217 G→A and T704C (M235T) variants on the risk of severe preeclampsia[J].J Renin Angiotensin Aldosterone Syst,2014,15(2):156-161.
[4] Aggarwal S,Dimri N,Tandon I,et al.Preeclampsia in North Indian women:the contribution of genetic polymorphisms[J].J Obstet Gynaecol Res,2011,37(10):1335-1341.
[5] Zafarmand MH,Franx A,Sabour S,et al.The M235T variant of the angiotensinogen gene is related to development of self-reported hypertension during pregnancy:the Prospect-EPIC cohort study[J].Hypertens Res,2008,31(7):1299-1305.
[6] Knyrim E,Muetze S,Eggermann T,et al.Genetic analysis of the angiotensinogen gene in pre-eclampsia:study of german women and review of the literature[J].Gynecol Obstet Invest,2008,66(3):203-208.
[7] 谢幸,孔北华,段涛,等.妇产科学[M].9版.北京:人民卫生出版社,2018:83-85.
[8] Russ AP,Maerz W,Ruzicka V,et al.Rapid detection of the hypertension associated Met235→Thr allele of the human angiotensinogen gene[J].Hum Mol Genet,1993,2(5):609-610.
[9] 朱旭明,郁昊达,孙伟峰,等.血管紧张素原基因T174M多态性与原发性高血压相关性的Meta分析[J].实用妇产科杂志,2013,29(4):639-641.
[10] Hasimu B,Nakayama T,Mizutani Y,et al.Haplotype analysis of human renin gene and essential hypertension[J].Hypertension,2003,41(2):308-312.
[11] Sethi AA,Nordestgaard BG,Agerholm-Larsen B,et al.Angiotensinogen polymorphisms and elevated blood pressure in the general population:the Copenhagen City Heart Study[J].Hypertension,2001,37(3):875-881.
[12] Wu CH,Wang Y,Ma M,et al.Antisense oligonucleotides targeting angiotensinogen:insights from animal studies[J].Biosci Rep,2019,39(1).pii:BSR20180201.
[13] Jeunemaitre X,Inoue I,WiIliams C,et al.Haplotypes of angiotensinogen in essential hypertension[J].Am J Hum Genet,1997,60(6):1448-1460.
[14] Zitouni H,Ben Ali Gannoum M,Raguema N,et al.Contribution of angiotensinogen M235T and T174M gene variants and haplotypes to preeclampsia and its severity in (North African) Tunisians[J].J Renin Angiotensin Aldosterone Syst,2018,19(1):1470320317753924.
[15] 宋成文,谢守珍,习波,等.血管紧张素原基因多态及血管生成因子与早发型重度子痫前期的相关性研究[J].实用医学杂志,2012,28(20):3338-3340.
[16] Jenkins LD,Powers RW,Cooper M,et al.Preeclampsia risk and angiotensinogen polymorphisms M235T and AGT -217 in African American and Caucasian women[J].Reprod Sci,2008,15(7):696-701.