The genetic susceptibility profile of type 2 diabetes and reflection of its possible role related to reproductive dysfunctions in the southern Indian population of Hyderabad

Abstract

Background The genetic association studies of type 2 diabetes mellitus (T2DM) hitherto undertaken among the Indian populations are grossly inadequate representation of the ethnic and geographic heterogeneity of the country. In view of this and due to the inconsistent nature of the results of genetic association studies, it would be prudent to undertake large scale studies in different regions of India considering wide spectrum of variants from the relevant pathophysiological pathways. Given the reproductive dysfunctions associated with T2DM, it would be also interesting to explore if some of the reproductive pathway genes are associated with T2DM. The present study is an attempt to examine these aspects in the southern Indian population of Hyderabad. Methods A prioritized panel of 92 SNPs from a large number of metabolic and reproductive pathway genes was genotyped on 500 cases and 500 controls, matched for ethnicity, age and BMI, using AGENA MassARRAYiPLEX™ platform. Results The allelic association results suggested 14 SNPs to be significantly associated with T2DM at P ≤ 0.05 and seven of those—rs2241766-G (ADIPOQ), rs6494730-T (FEM1B), rs1799817-A and rs2059806-T (INSR), rs11745088-C (FST), rs9939609-A and rs9940128-A (FTO)—remained highly significant even after correction for multiple testing. A great majority of the significant SNPs were risk in nature. The ROC analysis of the risk scores of the significant SNPs yielded an area under curve of 0.787, suggesting substantial power of our study to confer these genetic variants as predictors of risk for T2DM. Conclusions The associated SNPs of this study are known to be specifically related to insulin signaling, fatty acid metabolism and reproductive pathway genes and possibly suggesting the role of overlapping phenotypic features of insulin resistance, obesity and reproductive dysfunctions inherent in the development of diabetes. Large scale studies involving gender specific approach may be required in order to identify the precise nature of population and gender specific risk profiles for different populations, which might be somewhat distinct.

Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of type 2 diabetes mellitus and dyslipidemia, but not coronary artery disease in a Chinese Han population

“…In line with our findings, a series of studies have reported significant correlations of FTO rs9939609 and rs17817449 polymorphisms with the risk of T2DM and dyslipidemia (24,28,29,33,(46)(47)(48)(49)(50)(51). Younus et al conducted a case-control study to investigate the impact of the rs9939609 and rs17817449 polymorphisms on the development of T2DM in a sample of obese Iraqis, and found that the minor alleles of both variants are associated with an increased risk of T2DM (33).…”

“…Younus et al conducted a case-control study to investigate the impact of the rs9939609 and rs17817449 polymorphisms on the development of T2DM in a sample of obese Iraqis, and found that the minor alleles of both variants are associated with an increased risk of T2DM (33). In addition, the significant relation between the rs9939609 and rs17817449 polymorphisms and T2DM risk was reported in Vietnamese (28), Indians (29), Egyptians (47) and Czechs (48) and Pakistanis (51). Sierra-Ruelas and teammates explored the association of the rs9939609 variant with serum lipids among Mexican adults, and found that the A allele carriers had significantly higher levels of TC and LDL-C (24).…”

Signature pattern of gene expression and signaling pathway in premature diabetic patients uncover their correlation to early age coronary heart disease

“…The results analysis showed that the average age for the controls group was 54 and for patient groups were as follows: T2D (53), CHD (52), and T2D + CHD (53). Consequently, the different comparison of the mean age of both groups revealed no statistically significant differences between the groups: control, T2D, CHD, and T2D + CHD.…”

“…Phase 1 was conducted to determine the T2D risk genes in the Malaysian population. Previously, it was proved that the T2D risk genes were different in geographically distinct populations [52,53]. Furthermore, phase two was conducted to subtract coexisting genes in phases one and two from phase one because these dysregulated genes were intrinsically CHD risk genes.…”

Recent Progress in the Diagnosis and Management of Type 2 Diabetes Mellitus in the Era of COVID-19 and Single Cell Multi-Omics Technologies

“…Using the whole transcriptome RNAseq, the same group further investigated the peripheral subcutaneous adipose tissue of Asian Indians and found altered lipid, glucose, and protein metabolisms; adipogenesis defects; and inflammation associated with T2DM [ 183 ]. Using the AGENA MassARRAYiPLEX™ platform, Irgam et al recently identified seven significant SNPs (s2241766-G (ADIPOQ), rs6494730-T (FEM1B), rs1799817-A, rs2059806-T (INSR), rs11745088-C (FST), rs9939609-A, and rs9940128-A (FTO)) associated with T2DM in a southern Asian Indian population of 500 cases [ 184 ].…”