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旁遮普邦(印度西北部)2型糖尿病患者中TNF-α(g.-308 G > A)和ADIPOQ(g. + 45 T > G)基因多态性与微血管并发症

TNF-α (g.-308 G > A) and ADIPOQ (g. + 45 T > G) gene polymorphisms in type 2 diabetes and microvascular complications in the region of Punjab (North-West India).

作者信息

Sikka Ruhi, Raina Priyanka, Matharoo Kawaljit, Bandesh Khushdeep, Bhatia Rajan, Chakrabarti Subhabrata, Bhanwer A J S

机构信息

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

出版信息

Curr Eye Res. 2014 Oct;39(10):1042-51. doi: 10.3109/02713683.2014.892998. Epub 2014 Mar 21.

DOI:10.3109/02713683.2014.892998
PMID:24655058
Abstract

AIMS

The present study aims to examine the association of tumor necrosis factor-α (TNF-α) g.-308 G > A and adiponectin (ADIPOQ) g. + 45 T > G gene polymorphisms in type 2 diabetes (T2D) and its microvascular complications diabetic retinopathy (DR) and diabetic nephropathy (DN).

MATERIALS AND METHODS

A total of 672 individuals were analysed from the North-West population of Punjab. Genotyping was accomplished by a combination of allele specific amplification refractory mutation system and restriction digestion for TNF-α g. - 308 G > A and ADIPOQ g. + 45 T > G polymorphisms, respectively. Further, in silico modeling was done to predict secondary structure of mRNA for g. + 45 T > G polymorphism in the ADIPOQ gene by RNA fold.

RESULTS

The minor allele frequency observed in the controls for the TNF-α G > A and ADIPOQ T > G polymorphisms were 0.07 and 0.10, respectively. The results show no significant association with TNF-α g. - 308 G > A polymorphism in T2D as well as in any of the microvascular complication. However, the ADIPOQ g. + 45 T > G polymorphism shows significant association in T2D (p = 0.048) and DR (p = 0.001) but in DN patients, no association was observed. Interactive analysis revealed that the two polymorphisms jointly conferred a 1.45-fold risk towards the occurrence of T2D [p = 0.031; OR = 1.45 (1.03-2.05)]. In the secondary structure of mRNA, slight free energy change was observed between the wild ( - 1370.28 kcal/mol) and variant allele (-1369.08 kcal/mol).

CONCLUSIONS

Our results indicated a higher risk of T2D and DR in the background of ADIPOQ TT genotype. Further, the ADIPOQ g. + 45 T > G and TNF-α g. - 308 G > A polymorphisms jointly give 1.45-fold risk towards T2D.

摘要

目的

本研究旨在探讨2型糖尿病(T2D)及其微血管并发症糖尿病视网膜病变(DR)和糖尿病肾病(DN)中肿瘤坏死因子-α(TNF-α)基因g.-308 G > A多态性与脂联素(ADIPOQ)基因g. + 45 T > G多态性之间的关联。

材料与方法

对旁遮普邦西北部人群中的672名个体进行了分析。分别采用等位基因特异性扩增不应突变系统和限制性酶切法对TNF-α基因g. - 308 G > A多态性和ADIPOQ基因g. + 45 T > G多态性进行基因分型。此外,通过RNA fold软件对ADIPOQ基因g. + 45 T > G多态性的mRNA二级结构进行了计算机模拟预测。

结果

在对照组中观察到的TNF-α基因G > A多态性和ADIPOQ基因T > G多态性的次要等位基因频率分别为0.07和0.10。结果显示,TNF-α基因g. - 308 G > A多态性与T2D以及任何微血管并发症均无显著关联。然而,ADIPOQ基因g. + 45 T > G多态性在T2D(p = 0.048)和DR(p = 0.001)中显示出显著关联,但在DN患者中未观察到关联。交互分析显示,这两种多态性共同使T2D发生风险增加1.45倍[p = 0.031;OR = (1.45(1.03 - 2.05)]。在mRNA二级结构中,野生型(-1370.28 kcal/mol)和变异等位基因(-1369.08 kcal/mol)之间观察到轻微的自由能变化。

结论

我们的结果表明,在ADIPOQ基因TT基因型背景下,T2D和DR的风险更高。此外,ADIPOQ基因g. + 45 T > G多态性和TNF-α基因g. - 308 G > A多态性共同使T2D发生风险增加1.45倍。

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