糖尿病肾病患者触珠蛋白基因多态性及血清触珠蛋白浓度分析

doi:10.3969/j.issn.1006-7795.2023.03.003

首都医科大学学报 ›› 2023, Vol. 44 ›› Issue (3): 375-380.doi: 10.3969/j.issn.1006-7795.2023.03.003

• 内分泌研究与临床实践 • 上一篇下一篇

糖尿病肾病患者触珠蛋白基因多态性及血清触珠蛋白浓度分析

李雨阳¹，朱晓蓉¹，刘婧²，郑晓敏³，杨金奎^1,4*，杨芳远^1,4*

1. 首都医科大学附属北京同仁医院内分泌科，北京 100730；2. 北京市海淀医院感染性疾病科，北京 100080；3. 清华大学附属垂杨柳医院内分泌科，北京 100022；4. 北京市糖尿病研究所，北京 100730

收稿日期:2023-03-01 出版日期:2023-06-21 发布日期:2023-06-08
通讯作者: 杨金奎，杨芳远 E-mail:jkyang@ccmu.edu.cn; yangfangyuan@msn.com
基金资助:
国家自然科学基金面上项目（8151101058, 81930019），北京市属医院科研培育项目（PX2020008）

Analysis of haptoglobin gene polymorphisms and serum haptoglobin levels in patients with diabetes kidney disease

Li Yuyang¹, Zhu Xiaorong¹, Liu Jing², Zheng Xiaomin³, Yang Jinkui^1,4*, Yang Fangyuan^1,4*

1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; 2. Department of Infectious Disease, Beijing Haidian Hospital, Beijing 100080, China; 3. Department of Endocrinology, Chuiyangliu Hospital Affiliated to Tsinghua University, Beijing 100022, China; 4. Beijing Diabetes Institute, Beijing 100730, China

Received:2023-03-01 Online:2023-06-21 Published:2023-06-08
Supported by:
This study was supported by National Natural Science Foundation of China (8151101058, 81930019)， Beijing Municipal Administration of Hospitals Incubating Program (PX2020008).

摘要/Abstract

摘要： 目的本研究旨在探讨触珠蛋白（haptoglobin，Hp）基因多态性及血清Hp浓度与糖尿病肾病（diabetes kidney disease，DKD）的关系。方法在首都医科大学附属北京同仁医院内分泌科自2018年6月至2019年2月住院的2型糖尿病患者中，取212例单纯糖尿病患者为对照组，249例DKD患者为病例组。通过丙烯酰胺凝胶电泳（polyacrylamide gel electrophoresis，PAGE）和BN Ⅱ蛋白分析仪，检测患者的Hp基因型和血清Hp浓度。比较两组间Hp基因型频率、等位基因频率、血清Hp浓度及其他生物学指标，使用PRISM统计软件进行统计分析。结果研究结果显示，Hp1-1、Hp2-1和Hp2-2 3种基因型的频率分布在两组患者间差异无统计学意义（P=0.711）。病例组的血清Hp浓度显著高于对照组（P<0.05）。不同基因型受试者之间的血清Hp浓度存在明显差异，在两组受试者中，Hp1-1亚型的血清Hp浓度均最高，而 Hp2-2亚型的血清Hp浓度显著低于其他两种基因型（P<0.001）。相关性分析表明，血清Hp与血红蛋白浓度相关。结论 DKD患者的血清Hp浓度显著升高，但未发现Hp基因型与DKD之间存在显著关联，然而Hp基因型会影响循环Hp的含量。

关键词: 糖尿病, 糖尿病肾病, 触珠蛋白, 基因型

Abstract: Objective To investigate the relationship between haptoglobin (Hp) gene polymorphisms, serum Hp levels and diabetic kidney disease（DKD）. Methods Hp genotypes and serum Hp levels were detected by acrylamide gel electrophoresis (PAGE) and BN Ⅱ protein analyzer in 461 patients with type 2 diabetes, who were hospitalized in the Department of Endocrinology，Beijing Tongren Hospital，Capital Medical University from June 2018 to February 2019. The study subjects were divided into two groups: the control group patients with simple diabetes (212 cases) and the case group patients with complicated chronic kidney disease (249 cases). The frequency of haptoglobin genotype, allele frequency, serum haptoglobin level and other biological indicators were compared to each other between the two groups, and statistical analysis was performed using PRISM statistical software. Results The results showed that the frequency distribution of the three genotypes Hp1-1, Hp2-1 and Hp2-2 was not statistically different in the two groups (P=0.711). Serum Hp levels were significantly higher in the case group than that in the control group (P<0.05). There were significant differences in serum Hp levels among subjects of different genotypes. In both groups, the Hp1-1 subtype had the highest serum Hp concentration, while the Hp2-2 subtype had significantly lower serum Hp levels (P<0.001). Correlation analysis showed that there was a correlation between serum Hp and hemoglobin levels. Conclusion Serum Hp levels were significantly elevated in patients with diabetic chronic kidney disease, but no significant association was found between Hp genotype and DKD. However, Hp genotype may affect the content of circulating Hp.

Key words: diabetes mellitus, diabetes kidney disease, haptoglobin, genotype

中图分类号:

R587

李雨阳, 朱晓蓉, 刘婧, 郑晓敏, 杨金奎, 杨芳远. 糖尿病肾病患者触珠蛋白基因多态性及血清触珠蛋白浓度分析[J]. 首都医科大学学报, 2023, 44(3): 375-380.

Li Yuyang, Zhu Xiaorong, Liu Jing, Zheng Xiaomin, Yang Jinkui, Yang Fangyuan. Analysis of haptoglobin gene polymorphisms and serum haptoglobin levels in patients with diabetes kidney disease[J]. Journal of Capital Medical University, 2023, 44(3): 375-380.

参考文献

［1］Zhang L, Long J, Jiang W, et al. Trends in chronic kidney disease in China ［J］. N Engl J Med,2016，375(9): 905－906.
［2］Andersen C B F, Stdkilde K, Sderup K L, et al. Haptoglobin［J］. Antioxid Redox Signal,2017,26(14): 814－831.
［3］Dobryszycka W. Biological functions of haptoglobin--new pieces to an old puzzle［J］. Eur J Clin Chem Clin Biochem, 1997, 35(9): 647－654.
［4］Yang J K, Wang Y Y, Liu C, et al. Urine proteome specific for eye damage can predict kidney damage in patients with type 2 diabetes: a case-control and a 5.3-year prospective cohort study［J］. Diabetes Care, 2017, 40(2): 253－260.
［5］柯雨景, 董哲毅, 陈香美. 触珠蛋白与糖尿病肾病的关系研究进展［J］. 解放军医学杂志, 2021, 46(1): 84－88.
［6］Asleh R, Briasoulis A, Berinstein E M, et al. Meta-analysis of the association of the haptoglobin genotype with cardiovascular outcomes and the pharmacogenomic interactions with vitamin E supplementation［J］. Pharmgenomics Pers Med, 2018, 11: 71－82.
［7］Carter K, Worwood M. Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases［J］. Int J Lab Hematol,2007,29(2): 92－110.
［8］Nakhoul F M, Zoabi R, Kanter Y, et al. Haptoglobin phenotype and diabetic nephropathy［J］. Diabetologia, 2001, 44(5): 602－604.
［9］Bessa S S, Hamdy S M, Ali E M. Haptoglobin gene polymorphism in type 2 diabetic patients with and without nephropathy: an Egyptian study［J］. Eur J Intern Med, 2007, 18(6): 489－495.
［10］Conway B R, Savage D A, Brady H R, et al. Association between haptoglobin gene variants and diabetic nephropathy: haptoglobin polymorphism in nephropathy susceptibility［J］. Nephron Exp Nephrol, 2007, 105(3): e75－e79.
［11］Awadallah S, Hamad M. A study of haptoglobin phenotypes in patients with chronic renal failure［J］. Ann Clin Biochem, 2003, 40(Pt 6): 680－683.
［12］Amor AJ, Canivell S, Oriola J, et al. Haptoglobin genotype and risk of diabetic nephropathy in patients with type 1 diabetes mellitus: a study on a Spanish population［J］. Nefrologia, 2014, 34(2): 212－215.
［13］Wobeto V P, Garcia P M, Zaccariotto T R, et al. Haptoglobin polymorphism and diabetic nephropathy in Brazilian diabetic patients［J］. Ann Hum Biol, 2009, 36(4): 437－441.
［14］Loh P T, Toh M P, Molina J A, et al. Ethnic disparity in prevalence of diabetic kidney disease in an Asian primary healthcare cluster［J］. Nephrology (Carlton), 2015, 20(3): 216－223.
［15］Shi X, Sun L, Wang L, et al. Haptoglobin 2－2 genotype is associated with increased risk of type 2 diabetes mellitus in northern Chinese［J］. Genet Test Mol Biomarkers, 2012, 16(6): 563－568.
［16］Araki S, Haneda M, Sugimoto T, et al. Factors associated with frequent remission of microalbuminuria in patients with type 2 diabetes［J］. Diabetes, 2005, 54(10): 2983－2987.
［17］Miller Y I, Altamentova S M, Shaklai N. Oxidation of low-density lipoprotein by hemoglobin stems from a heme-initiated globin radical: antioxidant role of haptoglobin［J］. Biochemistry, 1997, 36(40): 12189－12198.
［18］龙雪. 结合珠蛋白清除血红蛋白作用及机制［J］. 国际检验医学杂志, 2011, 32(10): 1097－1099.
［19］Schaer D J, Buehler P W, Alayash A I, et al. Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins［J］. Blood, 2013, 121(8): 1276－1284.
［20］Nakata K, Saitoh R, Amano J, et al. Alteration of intracellular secretory acute phase response proteins expressed in human hepatocyte induced by exposure with interleukin-6［J］. Cytokine, 2012, 59(2): 317－323.
［21］Costacou T, Levy A P. Haptoglobin genotype and its role in diabetic cardiovascular disease［J］. J Cardiovasc Transl Res, 2012, 5(4): 423－435.
［22］Brosius F C, Pennathur S. How to find a prognostic biomarker for progressive diabetic nephropathy［J］. Kidney Int, 2013, 83(6): 996－998.
［23］Liao W L, Chang C T, Chen C C, et al. Urinary proteomics for the early diagnosis of diabetic nephropathy in Taiwanese patients［J］. J Clin Med, 2018, 7(12).
［24］Asleh R, Guetta J, Kalet-Litman S, et al. Haptoglobin genotype-and diabetes-dependent differences in iron-mediated oxidative stress in vitro and in vivo［J］. Circ Res, 2005, 96(4): 435－441.
［25］Ruiz M A, Shah B N, Ren G, et al. Haptoglobin 1 allele predicts higher serum haptoglobin concentration and lower multiorgan failure risk in sickle cell disease［J］. Blood Adv, 2022, 6(24): 6242－6248.
［26］Kasvosve I, Gomo Z A, Gangaidzo I T, et al. Reference range of serum haptoglobin is haptoglobin phenotype-dependent in blacks［J］. Clin Chim Acta, 2000, 296(1－2): 163－170.
［27］van Rijn H J, van der Wilt W, Stroes J W, et al. Is the turbidimetric immunoassay of haptoglobin phenotype-dependent?［J］. Clin Biochem, 1987, 20(4): 245－248.

[1]	冯晓彤, 柯静, 朱琳, 赵冬. 糖尿病视网膜病变的病理生理学研究进展[J]. 首都医科大学学报, 2023, 44(3): 420-423.
[2]	刘畅, 郭默宁, 袁颖超, 郑建鹏, 杨金奎. 2013至2018年北京地区1型糖尿病发病率性别差异及预测[J]. 首都医科大学学报, 2023, 44(3): 370-374.
[3]	郑晓敏, 李彬, 刘翠平, 周迎生, 崔丽梅. 老年2型糖尿病患者黎明现象的分析和对策[J]. 首都医科大学学报, 2023, 44(3): 400-406.
[4]	李明嘉, 赵苗妙, 杨金奎. 组织蛋白酶在糖尿病及糖尿病肾病作用机制中的研究进展[J]. 首都医科大学学报, 2023, 44(3): 413-419.
[5]	夏宁, 聂秀红, 王美平, 冯志红, 穆志静, 樊晓君. 阻塞性睡眠呼吸暂停与单纯鼾症患者的睡眠效率与糖尿病患病率的相关性研究[J]. 首都医科大学学报, 2023, 44(3): 487-496.
[6]	马玉茹, 袁仙仙, 郑薇, 刘程, 王佳, 李光辉. 妊娠早期血清游离脂肪酸水平与妊娠期糖尿病的关系[J]. 首都医科大学学报, 2023, 44(2): 265-271.

糖尿病肾病患者触珠蛋白基因多态性及血清触珠蛋白浓度分析

Analysis of haptoglobin gene polymorphisms and serum haptoglobin levels in patients with diabetes kidney disease

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

编辑推荐

Metrics

本文评价