血管紧张素转换酶和血管紧张素原基因多态性及其与青海妊娠高血压疾病的相关性

王茹; 庄文婷; 王香林; 李红荣; 李长兴; 孔德霞; 李建华

doi:10.16098/j.issn.0529-1356.2020.02.024

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解剖学报 ›› 2020, Vol. 51 ›› Issue (2) : 294-299. DOI: 10.16098/j.issn.0529-1356.2020.02.024

人类学

血管紧张素转换酶和血管紧张素原基因多态性及其与青海妊娠高血压疾病的相关性

王茹¹ 庄文婷¹王香林² 李红荣³ 李长兴¹孔德霞⁴ 李建华^1*

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Association between angiotensin converting enzyme and angiotensinogen gene polymorphisms and pregnancy-induced hypertension in Qinghai

WANG Ru¹ ZHUANG Wen-ting¹WANG Xiang-lin² LI Hong-rong³ LI Chang-xing¹ KONG De-xia⁴ LI Jian-hua^1*

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摘要

目的探讨血管紧张素转换酶(ACE)和血管紧张素原 (AGT) 基因表达、基因多态性与青海孕产妇妊娠高血压疾病的相关性。方法选择210例妊娠高血压患者（HDCP组）和220例正常孕妇（CK组），运用限制性内切酶片段长度多态性聚合酶链反应(PCR-RFLP)方法检测AGT M235T、ACE I/D 基因多态性。结果 CK组ACE基因 DD、ID、Ⅱ 所占比例分别为 28.18%、47.73%、24.09%,HDCP组分别为33.81%、51.90%、14.29%（P<0.05，故两组的ACE基因分布有差异），HDCP组和对照组ACE I/D多态性等位基因I和D频率分布有差异（P<0.05,HDCP组D等位基因频率高于对照组（χ2=5.188,P<0.05），ACE基因型分布符合Hardy-Weinberg遗传平衡（χ2=0.423，df=2,查表χ2 界值表，P＞0.05，达到遗传平衡）；CK组AGT基因 MM、MT、TT 所占比例分别为 24.09%、43.64%、32.27%，HDCP组分别为15.71%、42.86%、41.43%（P<0.05,故两组的AGT基因分布差异有统计学意义），HDCP组和对照组AGT M235T多态性等位基因M和T频率分布有差异性（P<0.05），HDCP组T等位基因频率高于对照组（χ2＝6.796，P<0.05），AGT基因型分布符合Hardy-Weinberg遗传平衡（χ2＝3.242，df=2，查表χ2界值表，P＞0.05，达到遗传平衡）。结论 ACE I/D多态性和AGT M235T多态性与青海省汉族妊娠期高血压疾病有关，D等位基因和T等位基因可能是妊娠高血压疾病的易感基因。

Abstract

Objective To investigate the relationship between angiotensin converting enzyme (ACE) and angiotensinogen (AGT) gene expression, gene polymorphism and pregnancy-induced hypertension in Qinghai. Methods A total of 210 pregnant hypertensive patients (HDCP group) and 220 normal pregnant women (CK group) were enrolled. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect AGT M235T and ACE I/D gene polymorphism. Results The proportions of ACE gene DD, ID, and Ⅱ in CK group were 28.15%, 47.73%, and 24.09%, respectively. The HDCP group was 33.81%, 51.90%, and 14.29%, respectively (P<0.05). The frequency distribution of ACE I/D polymorphic alleles I and D was different between HDCP group and CK group(P<0.05). D allele frequency was higher in HDCP group than in CK group (χ2=5.188, P<0.05). ACE genotype distribution was accorded with Hardy-Weinberg genetic balance(χ2=0.423, df=2, check table χ2 boundary value table, P>0.05, reach genetic balance). The proportions of MM, MT and TT in CK group was 24.09%, 43.64% and 32.27%, respectively. The HDCP group was 15.71%, 42.86%, and 41.43% respectively (P<0.05). HDCP group and CK group AGT M235T polymorphic alleles M and T frequency distribution were different (P<0.05). HDCP group T allele frequency was higher than the CK group(χ2=6.796, P<0.05). AGT gene were genotype distribution accorded with Hardy-Weinberg genetic balance (χ2=3.242, df=2, check table χ2 boundary value table, P>0.05, reaching genetic balance). Conclusion The ACE I/D polymorphism and AGT M235T polymorphism are associated with hypertensive disorder of pregnancy in Han nationality in Qinghai Province. D allele and T allele may be susceptible genes of pregnancy-induced hypertension.

导出引用

王茹庄文婷王香林李红荣李长兴孔德霞李建华. 血管紧张素转换酶和血管紧张素原基因多态性及其与青海妊娠高血压疾病的相关性[J]. 解剖学报. 2020, 51(2): 294-299 https://doi.org/10.16098/j.issn.0529-1356.2020.02.024

WANG Ru ZHUANG Wen-ting WANG Xiang-lin LI Hong-rong LI Chang-xing KONG De-xia LI Jian-hua. Association between angiotensin converting enzyme and angiotensinogen gene polymorphisms and pregnancy-induced hypertension in Qinghai[J]. Acta Anatomica Sinica. 2020, 51(2): 294-299 https://doi.org/10.16098/j.issn.0529-1356.2020.02.024

中图分类号： R3

参考文献

［1］ Le J. Obstetrics and Gynecology［M］.7th ed.Beijing: People’s Health Publishing House，2008: 92-101. (in Chinese)

乐杰. 妇产科学［M］.第7 版.北京: 人民卫生出版社，2008: 92-101.

［2］ Suzuki Y, Matsuura A, Yamamoto T. Management of pregnancy induced hypertension［J］. Nihon Rinsho Jap Jour Clin Med,2015,73(11):1897-1903.

［3］ Deng L, Fang BM. Clinical epidemiological analysis of hypertensive disorder complicating pregnancy［J］. Hainan Medical Journal,2015,26(17):2602-2603.（in Chinese）

邓莉, 方碧梅. 妊娠期高血压疾病的临床流行病学分析［J］.海南医学,2015,26(17):2602-2603.

［4］ Han Y, Xu YD. Gene polymorphism and hypertensive disorder during pregnancy ［J］. Journal of International Obstetrics and Gynecology, 2011,38(1):17-20.(in Chinese)

韩云,徐友娣.基因多态性与妊娠期高血压疾病［J］.国际妇产科学杂志, 2011,38(1):17-20.

［5］ Mata-Greenwood E, Blood AB, Sands LD, et al. A novel rodent model of pregnancy complications associated with genetically determined angiotensin-converting enzyme (ACE) activity［J］. Am J Physiol Endocrinol Metab, 2018, 315(1):E52-E62.

［6］ Rigat B, Hubert C，Corvol P, et al. PCR detection of the insersion/deletion polymorphsim of the human angiotension converting enzyme gene (DCP1)(dipeptidy 1 carboxypeptidase 1)［J］.Nucleic Acids Res,1992,20(6):1433.

［7］ Lindpaintner K, Pfeffer MA, Kreutz R, et al. A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease［J］.N Eng1 Med,1995,332(11):706-711.

［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］ Guo L, Zuo HJ. Advances in the etiology of pregnancy-induced hypertension［J］. Experimental and Laboratory Medicine, 2014,32(4):414-416.(in chinese)

郭玲，左慧君.妊娠高血压疾病病因学的研究进［J］.实验与检验医学，2014,32(4):414-416.

［10］ His W. Renin-angiotensin-aldosterone system in the pathogenesis of pregnancy-induced hypertension［J］. Exp Clini Endocrinol Diabetes, 2018, 126(6):362-366.

［11］ Xu Y, Zhang SZh, Wan Y, et al. Expression of angiotensinogen mRNA in hypothalamus of stress rats［J］.Journal of the Fourth Military Medical University,2002,4,23(7):596-598.(in Chinese)

徐永，张素珍，万瑜, 等.应激老鼠下丘脑血管紧张素原mRNA的表达［J］.第四军医大学学报,2002,4,23(7):596-598.

［12］ Mombouli J. ACE inhibition, endothelial function and coronary artery lesions: role of kinins and nitric oxide［J］. Drugs, 1997, 54(Suppl 5):12-22.

［13］ 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.

［14］ Nu JQ, Li HF, Shen ZhX, et al. Correlation between ACE gene and CYP gene polymorphism and hypertensive disorder complicating pregnancy［J］.Chinese Journal of Modern Medicine, 2010,20(4):535-543.(in chinese)

牛建清,李宏芬,沈志霞, 等.ACE基因和CYP基因多态性与妊娠期高血压疾病的相关性研究［J］.中国现代医学杂志,2010, 20(4):535-543.

［15］ González-Garrido JA, García-Sánchez JR, Tovar-Rodríguez JM, et al. Preeclampsia is associate with, ACE, I/D polymorphism, obesity and oxidative damage in Mexican women［J］. Pregnancy Hypertens, 2017,10:22-27.

［16］ Xu YY, Cai QH. Correlation between angiotensin-converting enzyme gene polymorphism and angiotensin in preeclampsia［J］.Jiangxi Medicine, 2012,47(10):849-851. (in Chinese)

徐颖颖，蔡庆华.子痫前期血管紧张素转换酶基因多态性与血管紧张素的相关性研究［J］.江西医药, 2012,47(10):849-851.

［17］ Kim YJ, Park MH, Park HS, et al.Associations of polymorphisms of the angiotensinogen M235 polymophism and insert-deletion polymorphism with preeclampsia in Korean women.［J］.Eur J Obstet Gyneeol Repred Biol,2004,116(1):48-51.

［18］ Galao AO,De SouzaLH, Da costa BE, et al. Angiotensin-converting enzyme gene polymophism in preeclampsia and normalpregnancy［J］.Am J Obstet Gynecol, 2004,191(3):821-834.

［19］ Bai H,Liu XH,Liu R,et al.Study on angiotensinogen and angiotensin Ⅰ invertase gene variation in Chinese patients with pregnancy-induced hypertension syndrome［J］.Journal of West China University of Medical Sciences,2002,33(2):233-245.(in Chinese)

白怀，刘兴会,刘瑞, 等.中国人妊娠高血压综合征患者血管紧张素原及血管紧张素Ⅰ转化酶基因变异的研究［J］.华西医大学报, 2002,33(2):233-245.

［20］ Ren M, Yang YX, Liu WJ, et al. Relationship between ACE gene insertion/deletion (I/D) polymorphism and essential hypertension in Han, Tibetan and Mongolian populations in Qinghai［J］.Journal of Qinghai Medical College,2016, 37(2):118123.(in Chinese)

任明, 杨永鑫, 刘维军, 等. 青海汉、藏、蒙古族人群ACE基因插入/缺失(I/D)多态性与原发性高血压关系［J］. 青海医学院学报, 2016, 37(2):118-123.

［21］ Ward K, Hata A, Jeunemaitre X, et al. A molecular variant of angiotensinogen associated with preeclampsia［J］. Nat Genet,1993, 4(1):59-61.

［22］ Bouba Ⅰ, Makrydimas G, Kalaitzidis R, et al. Interaction between the polymorphisms of the renin-angiotensin system in preeclampsia［J］. Eur J Obstet Gynecol Reprod Biol, 2003,110(1):8-11.

［23］ Aung M, Konoshita T, Moodley J, et al. Association of gene polymorphisms of four components of renin-angiotensin-aldosterone system and preeclampsia in south african black women［J］. Eur J Obstet Gynecol Reprod Biol, 2017, 215:180-187.

［24］ Zhang H, Li YX, Peng WJ, et al. The gene variants of maternal/fetal renin-angiotensin system in preeclampsia: a hybrid case-parent/mother-control study［J］. Sci Rep, 2017, 7(1):5087.