Correlation between KCNQ1 and KCNJ11 gene polymorphisms and type 2 and post-transplant diabetes mellitus in the Asian Indian population

Abstract

Type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) share a common pathophysiology. However, diabetes mellitus is a complex disease, and T2DM and PTDM have different etiologies. T2DM is a metabolic disorder, characterized by persistent hyperglycemia, whereas PTDM is a condition of abnormal glucose tolerance, with variable onset after organ transplant. The KCNQ1 and KCNJ11 gene encode potassium channels, which mediate insulin secretion from pancreatic β-cells, and KCN gene mutations are correlated with the development of diabetes. However, no studies have been carried out to establish an association between KCNQ1 and KCNJ11 gene polymorphisms and T2DM and PTDM. Therefore, our study was aimed at the identification of the role of KCNQ1 and KCNJ11 gene polymorphisms associated with T2DM and the risk of developing PTDM in the Asian Indian population. We have carried out a case–control study including 250 patients with T2DM, 250 control subjects, 42 patients with PTDM and 98 subjects with non-PTDM. PCR-RFLP analysis was carried out following the isolation of genomic DNA from EDTA-blood samples. The results of the present study reveal that two single nucleotide polymorphisms (rs2283228 and rs5210, of the KCNQ1 and KCNJ11 genes, respectively) are associated with both T2DM and PTDM. The results of our study suggest a role of KCNQ1 and KCNJ11 gene variants in the increased risk of T2DM and PTDM in the Asian Indian population.

Importance of glucokinase -258G/A polymorphism in Asian Indians with post-transplant and type 2 diabetes mellitus

“…The selection of T2DM subjects, controls, and PTDM subjects and the inclusion and exclusion criteria for the specific groups are described in previous publications (1,5,11). We collected 3 mL of serum for biochemical analysis and 2 mL of anticoagulated blood for mutational analysis.…”

“…PTDM, also known as new-onset diabetes after transplantation (NODAT), is a frequent complication in renal transplant (RT) patients who receive immunosuppressive therapy with calcineurin inhibitors (4). Recipients with PTDM/NODAT and non-PTDM receive immunosuppressive drugs such as cyclosporine (CsA) and Tacrolimus (Tac) after renal transplantation and exhibit complications similar to those of T2DM patients in the general population, but with an accelerated rate of onset (5,6). Previous investigations have focused on candidate genes expressed in pancreatic β-cells that modulate insulin secretion and resistance and predispose individuals to PTDM and T2DM in later life.…”

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

“…RsaI (GT^AC) enzyme was used to detect the rs7903146 polymorphism and HpaII (C^CGG) enzyme for rs13266634 polymorphism. The protocol for PCR-RFLP analysis was described previously (3). The digested PCR products were separated by 3.5% agarose gel electrophoresis.…”

“…Tacrolimus (FK506, Tac) and cyclosporine A (CsA) are immunosuppressive drugs commonly used in the treatment after organ transplantation (2). Both PTDM and type 2 diabetes mellitus (T2DM) are multifactorial metabolic disorders (3). T2DM is a chronic disease, characterized by insulin resistance and impaired insulin secretion from pancreatic β-cells (4).…”

“…The appearance of family history of diabetes in predicting PTDM is still query and the relation for the risk factors of PTDM in the general population both from a common mechanistic viewpoint and from a practical viewpoint is unclear (7).Genome-wide studies have identified diabetes susceptibility loci on chromosomes 10q25.3 and 8q24.11, where transcription factor 7 like 2 (TCF7L2) and solute carrier member 3 zinc transporter member 8 (SLC30A8) genes are located (3). Earlier studies at the same genetic polymorphisms (TCF7L2-rs7903146 and SLC30A8-rs13266634) in PTDM subjects (8,9).…”