No detectable association of IGF2BP2 and SLC30A8 genes with type 2 diabetes in the population of Hyderabad, India

Abstract

Genome-wide association studies identified novel genes associated with T2DM which have been replicated in different populations. We try to examine here if certain frequently replicated SNPs of Insulin growth factor 2 m-RNA binding protein 2 (IGF2BP2) (rs4402960, rs1470579) and Solute Carrier family 30 member 8 (SLC30A8) (rs13266634) genes, known to be implicated in insulin pathway, are associated with T2DM in the population of Hyderabad, which is considered to be a diabetic capital of India. Genotyping of the 1379 samples, 758 cases and 621 controls, for the SNPs was performed on sequenom massarray platform. The logistic regression analysis was done using SPSS software and the post-hoc power of the study was estimated using G power. The allele and genotype frequencies were similar between cases and controls, both for SNPs of IGF2BP2 and SLC30A8 genes. Logistic regression did not reveal significant allelic or genotypic association of any of the three SNPs with T2DM. Despite large sample size and adequate power, we could not replicate the association of IGF2BP2 and SLC30A8 SNPs with T2DM in our sample from Hyderabad (A.P.), India, albeit another study based on much larger sample but from heterogeneous populations from the northern parts of India showed significant association of two of the above 3 SNPs, suggesting variable nature of susceptibility of these genes in different ethnic groups. Although the IGF2BP2 and SLC30A8 genes are important in the functional pathway of Insulin secretion, it appears that these genes do not play a significant role in the susceptibility to T2DM in this population.

Validation of the association of <i>TCF7L2</i> and <i>SLC30A8</i> gene polymorphisms with post-transplant diabetes mellitus in Asian Indian population

“…Our studies showed positive association towards rs7903146 and rs13266634 polymorphisms and not in accordance with the prior studies carried out in PTDM subjects in different ethnicities (9,15,21). The associations of diabetic diseases with rs7903146 and rs13266634 polymorphisms have been carried in Indian population (14,(22)(23)(24)(25)(26)(27)(28)(29). Our results showed the positive association between rs7903146 polymorphism and T2DM (submitted for publication) and GDM (unpublished).…”

“…synthesis, storage, and secretion (14). Previous studies showed no association of rs13266634 polymorphism with PTDM in different ethnicities (9,15,21), as well with T2DM in Indian population (25,28). Chauhan et al, (27) and our earlier study (14) showed a positive association of rs13266634 polymorphism with PTDM.…”

“…The rs13266634 is an amino acid substitution (TryptophanArginine) polymorphism most commonly associated with T2DM. The C325T missense variant is present in SLC30A8 gene, product of which belongs to zinc transporter family involved in Insulin secretion (25). It plays a major role in transporting zinc from the cytoplasm to intracellular insulin-containing vesicles for insulin maturation, storage, and secretion from pancreatic β-cells (37).…”

Association between IGF2BP2 Polymorphisms and Type 2 Diabetes Mellitus: A Case–Control Study and Meta-Analysis

“…For the rs4402960, 34 articles were available, including 49,974 cases and 54,315 controls in total. For the rs1470579, 14 articles involved 23,470 cases and 23,671 controls in total [ 12 , 15 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ] ( Table S3 ; Figure 1 ).…”

Some dietary factors can modulate the effect of the zinc transporters 8 polymorphism on the risk of metabolic syndrome

“…In some of these studies, this SNP (C allele) was associated with a higher risk of type-II diabetes (T2D), the MetS or its components 4, 5 , a relationship not seen in other studies 6, 7 , which explains only approximately 10% of the overall heritable risk of T2D. This contradiction among the study results and the inability of ZNT8 gene to fully explain the overall heritable risk of T2D 8 indicates the existence of a complex interaction among rs13266634 and environmental factors e.g.…”