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2型糖尿病患者大麻素受体-1基因多态性与糖尿病肾病风险的关联

Association Between Cannabinoid Receptor-1 Gene Polymorphism and the Risk of Diabetic Nephropathy Among Patients with Type 2 Diabetes Mellitus.

作者信息

Zhang Xuelian, Zhu Haiqing, Xing Xiaoyan, Zhang Chunyu

机构信息

Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.

Department of Endocrinology, Emergency General Hospital, Beijing 100028, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2020 Nov 12;13:591-599. doi: 10.2147/PGPM.S278897. eCollection 2020.

Abstract

BACKGROUND

The cannabinoid receptor 1 (CNR1) gene polymorphism is reportedly associated with components of metabolic syndrome and coronary artery diseases in patients with type 2 diabetes mellitus (T2DM). We investigated whether the common variant rs10493353 polymorphism is associated with diabetic nephropathy (DN) in T2DM patients.

PATIENTS AND METHODS

T2DM patients with DN were enrolled as a case group, and patients with only T2DM as a control group. Demographic data and biochemical parameters were collected. The polymerase chain reaction-based restriction fragment length polymorphism technique was used for genotyping. The odds ratio and 90% confidence interval were calculated to assess the association between genotypes and the risk of DN.

RESULTS

In total, 320 T2DM patients and 320 DN patients were enrolled. Compared with T2DM patients, the DN patients have a significantly larger body mass index (BMI), longer duration of disease, and higher proportions of smokers, drinkers, and hypertension. The risk of DN was significantly decreased by genotypes AA (OR=0.39, 95% CI=0.23-0.67) and GA (OR=0.53, 95% CI=0.37-0.75) vs GG (codominant model), GA/AA vs GG (OR=0.49, 95% CI=0.35-0.67; dominant model), AA vs GG/GA (OR=0.47, 95% CI=0.28-0.80; recessive model), and the A allele (OR=0.52, 95% CI=0.40-0.68; allele model). Multiple logistic regressions still show significant levels. Negative interactions were found between gene and clinical parameters, including drinking, smoking, BMI, and hypertension.

CONCLUSION

The A allele of CNR1 gene rs10493353 may be a protective factor for DN in T2DM patients. The risk factors of DN can affect the protective role of A allele in the progression of DN.

摘要

背景

据报道,大麻素受体1(CNR1)基因多态性与2型糖尿病(T2DM)患者的代谢综合征成分和冠状动脉疾病有关。我们研究了常见变异rs10493353多态性是否与T2DM患者的糖尿病肾病(DN)相关。

患者与方法

将患有DN的T2DM患者纳入病例组,仅患有T2DM的患者作为对照组。收集人口统计学数据和生化参数。采用基于聚合酶链反应的限制性片段长度多态性技术进行基因分型。计算比值比和90%置信区间,以评估基因型与DN风险之间的关联。

结果

共纳入320例T2DM患者和320例DN患者。与T2DM患者相比,DN患者的体重指数(BMI)显著更高,病程更长,吸烟者、饮酒者和高血压患者的比例更高。与GG基因型相比,AA基因型(OR=0.39,95%CI=0.23-0.67)和GA基因型(OR=0.53,95%CI=0.37-0.75)(共显性模型)、GA/AA与GG相比(OR=0.49,95%CI=0.35-0.67;显性模型)、AA与GG/GA相比(OR=0.47,95%CI=0.28-0.80;隐性模型)以及A等位基因(OR=0.52,95%CI=0.40-0.68;等位基因模型)使DN风险显著降低。多因素逻辑回归仍显示显著水平。在基因与临床参数(包括饮酒、吸烟、BMI和高血压)之间发现了负相互作用。

结论

CNR1基因rs10493353的A等位基因可能是T2DM患者发生DN的保护因素。DN的危险因素可影响A等位基因在DN进展中的保护作用。

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