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[TCF7L2、FABP2、KCNQ1、ADIPOQ基因多态性与2型糖尿病发生发展预后的相关性]

[Association of polymorphisms of genes TCF7L2, FABP2, KCNQ1, ADIPOQ with the prognosis of the development of type 2 diabetes mellitus].

作者信息

Mel'nikova E S, Rymar O D, Ivanova A A, Mustafina S V, Shapkina M J, Bobak M, Maljutina S K, Voevoda M I, Maksimov V N

机构信息

Research Institute of Internal and Preventive Medicine.

Department of Epidemiology & Public Health, University College London.

出版信息

Ter Arkh. 2020 Nov 24;92(10):40-47. doi: 10.26442/00403660.2020.10.000393.

Abstract

AIM

To study the possibility of using polymorphisms of genesTCF7L2,FABP2,KCNQ1,ADIPOQas markers for predicting the development of type 2 diabetes mellitus (T2D) in the population of Novosibirsk.

MATERIALS AND METHODS

On the basis of prospective observation of a representative population sample of residents of Novosibirsk (HAPIEE), 2 groups were formed according to the case-control principle (case people who had diabetes mellitus 2 over 10 years of observation, and control people who did not developed disorders of carbohydrate metabolism). T2D group (n=443, mean age 56.26.7 years, men 29.6%, women 70.4%), control group (n=532, mean age 56.17.1 years, men 32.7%, women 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package.

RESULTS AND DISCUSSION

No significant effect of rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene, and rs6773957 of theADIPOQgene on the risk of developing T2D was found. Genotypes TT and TC rs7903146 of theTCF7L2gene are genotypes for the risk of developing T2D (relative risk RR 3.90, 95% confidence interval CI 2.316.61,p0.001; RR 1.86, 95% CI 1.422.43,p0.001, respectively). The CC genotype rs7903146 of theTCF7L2gene is associated with a protective effect against T2D (RR 0.37, 95% CI 0.290.49,p0.001). When theTCF7L2gene is included in the model for assessing the risk of developing T2D rs7903146, it retains its significance in both men and women.

CONCLUSION

The rs7903146 polymorphism of theTCF7L2gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk meter. Variants of risk meters have been developed to assess the prognosis of the development of diabetes mellitus 2 in men and women aged 4569 years during 10 years of follow-up. The association with the prognosis of the development of T2D polymorphisms rs1799883 of theFABP2gene, rs2237892 of theKCNQ1gene and rs6773957 of theADIPOQgene was not found.

摘要

目的

研究使用基因TCF7L2、FABP2、KCNQ1、ADIPOQ的多态性作为预测新西伯利亚人群2型糖尿病(T2D)发病的标志物的可能性。

材料与方法

基于对新西伯利亚居民代表性人群样本(HAPIEE)的前瞻性观察,根据病例对照原则形成2组(病例组为在10年观察期内患有2型糖尿病的人,对照组为未发生碳水化合物代谢紊乱的人)。T2D组(n = 443,平均年龄56.2±6.7岁,男性29.6%,女性70.4%),对照组(n = 532,平均年龄56.1±7.1岁,男性32.7%,女性67.3%)。通过酚 - 氯仿提取法分离DNA。采用聚合酶链反应方法进行基因分型,随后进行限制性片段长度多态性分析、实时聚合酶链反应。使用SPSS 16.0软件包进行统计处理。

结果与讨论

未发现FABP2基因的rs1799883、KCNQ1基因的rs2237892和ADIPOQ基因的rs6773957对T2D发病风险有显著影响。TCF7L2基因的rs7903146的TT和TC基因型是T2D发病风险的基因型(相对风险RR 3.90,95%置信区间CI 2.31 - 6.61,p < 0.001;RR 1.86,95% CI 1.42 - 2.43,p < 0.001)。TCF7L2基因的rs7903146的CC基因型与对T2D的保护作用相关(RR 0.37,95% CI 0.29 - 0.49,p < 0.001)。当将TCF7L2基因的rs7903146纳入评估T2D发病风险的模型时,它在男性和女性中均保持其显著性。

结论

TCF7L2基因的rs7903146多态性证实了其与T2D发病预后的关联,这表明有可能将其视为纳入糖尿病风险评估指标的候选基因。已开发出风险评估指标变体,用于评估45 - 69岁男性和女性在10年随访期间2型糖尿病发病的预后。未发现FABP2基因的rs1799883、KCNQ1基因的rs2237892和ADIPOQ基因的rs6773957多态性与T2D发病预后的关联。

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