ApoE基因多态性与ADMA水平在慢性肾脏病患者中的关联研究

doi:10.3760/cma.j.issn.1007-1245.2022.08.003

国际医药卫生导报 ›› 2022, Vol. 28 ›› Issue (8): 1047-1052.DOI: 10.3760/cma.j.issn.1007-1245.2022.08.003

ApoE基因多态性与ADMA水平在慢性肾脏病患者中的关联研究

梅佳慧娄焕堃王勋韩翠敏李鹏邢团结汪明琅王怡练

蚌埠医学院附属连云港市第二人民医院心血管内科，连云港　222006

收稿日期:2021-05-06 出版日期:2022-04-15 发布日期:2022-05-09
通讯作者: 王怡练，Email：497857934@qq.com
基金资助:
江苏省“六大人才高峰”高层次人才选拔培养项目（WSN-247）；

江苏大学临床医学科技发展基金项目（JLY2021086）

Association between ApoE gene polymorphism and ADMA level in patients with chronic kidney disease

Mei Jiahui, Lou Huankun, Wang Xun, Han Cuimin, Li Peng, Xing Tuanjie, Wang Minglang, Wang Yilian

Department of Cardiovascular Medicine, Lianyungang Second People's Hospital Affiliated to Bengbu Medical College, Lianyungang 222006, China

Received:2021-05-06 Online:2022-04-15 Published:2022-05-09
Contact: Wang Yilian, Email: 497857934@qq.com
Supported by:
"Six Talent Peak" High-Level Talent Selection and Training Project of Jiangsu Province (WSN-247);

Clinical Medical Science and Technology Development Fund Project of Jiangsu University (JLY2021086)

摘要/Abstract

摘要： 目的　探讨慢性肾脏病患者载脂蛋白E（ApoE）基因多态性与不对称二甲基精氨酸（ADMA）水平的表达及其关联性。方法　选择2018年1月至2020年1月在连云港市第二人民医院心内科、肾内科住院的慢性肾脏病患者300例，采用慢性肾脏疾病流行病学协作（CKD-EPI）方法计算肾小球滤过率（GFR），按GFR对300例患者进行分组：Ⅰ组GFR >60 ml/min（86例），Ⅱ组15 ml/min <GFR ≤60 ml/min（119例），Ⅲ组GFR ≤15 ml/min或血液透析患者（95例）。用聚合酶链反应扩增法（PCR）检测ApoE基因多态性，采用酶联免疫吸附双抗体夹心法（ELISA）检测ADMA水平，比较各组等位基因和基因型分布。计量资料组间比较采用方差分析，计数资料比较采用χ²检验。结果　300例患者年龄（61.9±13.1）岁，男性151例（50.33%），体质量指数（BMI）（28.0±5.1）kg/m²，糖尿病88例（29.33%），心血管疾病174例（58.00%）。3组间糖尿病、冠心病比例及低密度脂蛋白、三酰甘油、肌酐、ADMA水平比较，差异均有统计学意义（均P<0.05）。ApoEε2等位基因35例（11.67%），ε3等位基因287例（95.67%），ε4等位基因58例（19.33%）。ApoE等位基因在不同肾功能分组中分布是均一的（均P>0.05）；基于ADMA水平分组，ApoE基因多态性在不同ADMA水平组的分布中差异均有统计学意义（均P<0.05）。结论　随着GFR的降低，血浆ADMA水平显著升高；ApoE等位基因在不同肾功能分组中分布是均一的；ApoE等位基因在不同ADMA水平分组中分布是不均一的；肾功能异常等临床变量的存在限制了ApoEε4等位基因的表达。

关键词: 不对称二甲基精氨酸, 载脂蛋白E, 基因多态性, 动脉粥样硬化, 慢性肾脏疾病

Abstract: Objective　To investigate the association between apolipoprotein E (ApoE) gene polymorphism and asymmetric dimethylarginine (ADMA) expression in patients with chronic kidney disease. Methods　A total of 300 patients with chronic kidney disease hospitalized in the departments of cardiology and nephrology of Lianyungang Second People's Hospital from January 2018 to January 2020 were selected. The glomerular filtration rate (GFR) was calculated by the chronic kidney disease epidemiology collaboration (CKD-EPI) method, and 300 patients were stratified according to the GFR: group I with GFR >60 ml/min (86 cases), group Ⅱ with GFR >15 ml/min and ≤60 ml/min (119 cases), and group III with GFR ≤15 ml/min or hematodialysis (95 cases). The ApoE gene polymorphism was detected by polymerase chain reaction (PCR) amplification method, and the ADMA level was detected by double antibody sandwich enzyme-linked immunosorbent method (ELISA). The alleles and genotypes of each group were compared. ANOVA was used for comparison of the measurement data between groups, and χ² test was used for comparison of the count data. Results　The 300 patients were (61.9±13.1) years old, with 151 males (50.33%), body mass index (BMI) of (28.0±5.1) kg/m², including 88 cases (29.33%) of diabetes and 174 cases (58.00%) of cardiovascular diseases. There were statistically significant differences in the proportions of diabetes and coronary heart disease and the levels of low density lipoprotein, triglyceride, creatinine, and ADMA among the three groups (all P<0.05). There were 35 cases (11.67%) of ApoEε2 allele, 287 cases (95.67%) of ApoEε3 allele, and 58 cases (19.33%) of ApoEε4 allele. Based on the renal function, allele distribution was uniform among the three groups (all P>0.05); based on the ADMA level, the distribution of ApoE gene polymorphism was different in different ADMA level groups (all P<0.05). Conclusions　With the decrease of the GFR, the plasma ADMA level increases significantly. The distribution of ApoE alleles is uniform among different renal function groups. The distribution of ApoE alleles is not uniform in different ADMA level groups. The presence of clinical variables such as renal dysfunction limits the expression of ApoEε4 allele.

Key words: Asymmetric dimethylarginine, Apolipoprotein E, Gene polymorphism, Atherosclerosis, Chronic kidney disease

梅佳慧, 娄焕堃, 王勋, 韩翠敏, 李鹏, 邢团结, 汪明琅, 王怡练.

ApoE基因多态性与ADMA水平在慢性肾脏病患者中的关联研究 [J]. 国际医药卫生导报, 2022, 28(8): 1047-1052.

Mei Jiahui, Lou Huankun, Wang Xun, Han Cuimin, Li Peng, Xing Tuanjie, Wang Minglang, Wang Yilian. Association between ApoE gene polymorphism and ADMA level in patients with chronic kidney disease[J]. International Medicine and Health Guidance News, 2022, 28(8): 1047-1052.

参考文献

[1] Vallance P, Leone A, Calver A, et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure[J].Lancet,1992,339(8793):572-575. DOI:10.1016/0140-6736(92)90865-z.

[2] 袁美杰,吴明,叶朝阳. 不对称二甲基精氨酸在慢性肾脏病中的作用与机制研究进展[J]. 中国血液净化,2020,19(5):327-329.DOI:10.3969/j.issn.1671-4091. 2020.05.011.

[3] 刘国栋,王桦,汪琦,等. APOE基因多态性与血脂异常相关性分析[J]. 武汉大学学报(医学版),2017,38(2):267-270. DOI:10.14188/j.1671-8852.2017.02.020.

[4] Boerwinkle E, Visvikis S, Welsh D, et al. The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals[J]. Am J Med Genet,1987,27(3):567-582. DOI:10.1002/ajmg. 1320270310.

[5] 梁爱芬,何韶坚,华仙丽,等. ApoE基因多态性与慢性心血管疾病及患者血脂水平的相关性研究[J]. 国际检验医学杂志,2017,38(12):1601-1602,1605. DOI:10.3969/j.issn.1673- 4130. 2017. 12.006.

[6] Wieczorek-Surdacka E, Hanff E, Chyrchel B, et al. Distinct associations between plasma osteoprotegerin, homoarginine and asymmetric dimethylarginine in chronic kidney disease male patients with coronary artery disease[J].Amino Acids,2019,51(6):977-982. DOI:10.1007/s00726- 019-02738-x.

[7] Ravani P, Tripepi G, Malberti F, et al. Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach[J].J Am Soc Nephrol,2005,16(8):2449-2455. DOI:10.1681/ASN.2005010076.

[8] Wang C, Jiang H, Jin J, et al. Development of potent type I protein arginine methyltransferase (PRMT) inhibitors of leukemia cell proliferation[J].J Med Chem,2017,60(21):8888-8905. DOI:10.1021/acs.jmedchem.7b01134.

[9] 温佐强,魏昕,方才. 不对称二甲基精氨酸和内皮细胞功能紊乱及相关疾病的关系[J]. 安徽医药,2009,13(1):13-15. DOI:10.3969/j.issn.1009-6469.2009.01.006.

[10] Sibal L, Agarwal SC, Home PD, et al. The role of asymmetric dimethylarginine (ADMA) in endothelial dysfunction and cardiovascular disease[J].CurrCardiol Rev,2010,6(2):82-90. DOI:10.2174/157340310791162659.

[11] Park MJ, Oh KS, Nho JH, et al. Asymmetric dimethylarginine (ADMA) treatment induces apoptosis in cultured rat mesangial cells via endoplasmic reticulum stress activation[J].Cell Biol Int,2016,40(6):662-670. DOI:10.1002/cbin.10602.

[12] Zhou TB, Qin YH, Xu HL. Association of apoE gene expression and its gene polymorphism with nephrotic syndrome susceptibility: a meta-analysis of experimental and human studies[J].MolBiol Rep,2012,39(10):9347-9354. DOI:10.1007/s11033-012-1751-4.

[13] 胡耀,谭昀,桂绍涛,等. 高血脂病人载脂蛋白E基因多态性与心肌梗死相关性[J]. 安徽医药,2020,24(9):1753-1756. DOI:10.3969/j.issn.1009-6469.2020.09.014.

[14] 董政,娄焕堃,梅佳慧,等. 载脂蛋白E基因多态性与炎症的相关性研究进展[J]. 中国临床实用医学,2020,11(5):74-77. DOI:10.3760/cma.j.cn115570-20200715.01006.

[15] 汪明琅,娄焕堃,王飞翔,等. ApoE基因多态性与心房颤动的相关性研究[J]. 国际医药卫生导报,2019,25(22):3680-3684. DOI:10.3760/cma.j.issn.1007-1245.2019. 22.006.

[16] Bennet AM, Di Angelantonio E, Ye Z, et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk[J].JAMA,2007,298(11):1300-1311. DOI:10.1001/jama.298.11.1300.

[17] 张秀玲. 山东汉族人群ApoE基因多态性与房颤的相关性[D]. 济南:山东大学,2017.

[18] Liberopoulos E, Siamopoulos K, Elisaf M. Apolipoprotein E and renal disease[J].Am J Kidney Dis,2004,43(2):223-233. DOI:10.1053/j.ajkd.2003.10.013.

[19] Xue C, Nie W, Tang D, et al. Apolipoprotein E gene variants on the risk of end stage renal disease[J].PLoS One,2013,8(12):e83367. DOI:10.1371/journal.pone.0083367.

[20] Hubacek JA, Bloudickova S, Kubinova R, et al. Apolipoprotein E polymorphism in hemodialyzed patients and healthy controls[J].Biochem Genet,2009,47(9-10):688-693. DOI:10.1007/s10528-009-9266-y.

[21] Roussos L, Ekström U, Ehle PN, et al. Apolipoprotein E polymorphism in 385 patients on renal replacement therapy in Sweden[J].Scand J Urol Nephrol,2004,38(6):504-510. DOI:10.1080/00365590410033443.

ApoE基因多态性与ADMA水平在慢性肾脏病患者中的关联研究

Association between ApoE gene polymorphism and ADMA level in patients with chronic kidney disease

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