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载脂蛋白基因单核苷酸多态性-3971G/A 和+276G/T 与北印度旁遮普邦 2 型糖尿病的关联研究。

Association study of the single-nucleotide polymorphisms -3971G/A and +276G/T in the adiponectin gene with type 2 diabetes in a North Indian Punjabi population.

机构信息

Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India.

出版信息

Ann Hum Genet. 2020 May;84(3):235-248. doi: 10.1111/ahg.12366. Epub 2019 Nov 21.

Abstract

OBJECTIVE

To investigate the role of ADIPOQ gene variants (-3971G/A rs822396 and +276G/T rs1501299) with type 2 diabetes risk in a North Indian Punjabi population.

METHODS

Adiponectin is one of the most abundant circulating adipocytokines in the human body that plays an important role in the metabolic processes and positively regulates energy homeostasis and insulin secretion. Several studies have provided the evidence of adiponectin gene polymorphisms association with type 2 diabetes mellitus (T2DM) in different ethnic populations. A total of 616 subjects including 316 T2DM patients and 300 normal healthy controls from Punjab were genotyped for ADIPOQ polymorphisms (rs822396 and rs1501299) by using a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Anthropometric, physiometric, and biochemical measurements were taken from each participant.

RESULTS

Genotypic frequencies were significantly different in T2DM subjects and healthy controls for both polymorphisms (rs822396 and rs1501299). The risk genotype GG of -3971A/G and TT of +276G/T conferred an approximately twofold risk towards the development of T2DM and were found to be significantly higher in T2DM cases than control subjects (p = 0.006 and p = 0.019, respectively, after the Bonferroni correction). The recessive model of the ADIPOQ polymorphism rs822396 was significantly shown to confer a 3.63-fold risk towards type 2 diabetes after adjusting for confounding factors and Bonferroni correction [odds ratio (OR): 3.63 (1.20-10.96), p = 0.022]. rs1501299 gave a 3.82-fold risk towards development of T2DM but was not statistically significant after Bonferroni correction [OR: 3.82 (1.16-12.55), p = 0.027]. Meta-analysis also illustrated the overall effect of the minor allele of rs822396 (-3971A/G) polymorphism, providing a greater risk for the T2DM development.

CONCLUSION

Thus, we concluded on the basis of observed results that the ADIPOQ gene polymorphisms rs822396 and rs1501299 plays an important role in the development of type 2 diabetes in North Indian Punjabi population.

摘要

目的

研究 ADIPOQ 基因变异(-3971G/A rs822396 和 +276G/T rs1501299)在北印度旁遮普人群 2 型糖尿病风险中的作用。

方法

脂联素是人体内最丰富的循环脂肪细胞因子之一,在代谢过程中发挥重要作用,并正向调节能量稳态和胰岛素分泌。多项研究提供了证据表明,脂联素基因多态性与不同种族人群的 2 型糖尿病(T2DM)有关。共纳入 616 名受试者,包括 316 名 T2DM 患者和 300 名正常健康对照者,来自旁遮普邦,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对 ADIPOQ 多态性(rs822396 和 rs1501299)进行基因分型。对每位参与者进行人体测量、生理和生化测量。

结果

在 T2DM 患者和健康对照组中,两种多态性(rs822396 和 rs1501299)的基因型频率均存在显著差异。-3971A/G 的风险基因型 GG 和+276G/T 的 TT 使 T2DM 的发病风险增加约两倍,且在 T2DM 病例中明显高于对照组(p = 0.006 和 p = 0.019,分别在 Bonferroni 校正后)。ADIPOQ 多态性 rs822396 的隐性模型在调整混杂因素和 Bonferroni 校正后,显著显示出 3.63 倍的 2 型糖尿病发病风险[比值比(OR):3.63(1.20-10.96),p = 0.022]。rs1501299 使 T2DM 的发病风险增加 3.82 倍,但在 Bonferroni 校正后无统计学意义[OR:3.82(1.16-12.55),p = 0.027]。荟萃分析还说明了 rs822396(-3971A/G)多态性的次要等位基因的总体效应,为 T2DM 的发展提供了更大的风险。

结论

因此,我们根据观察结果得出结论,ADIPOQ 基因多态性 rs822396 和 rs1501299 在外印度旁遮普人群 2 型糖尿病的发生发展中起着重要作用。

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