Meta-analysis indicated significant association between the IGF2BP2 rs4402960 and CDKAL1rs7756992 polymorphisms and increased risk of diabetes in Arab populations.
Taken together, our findings provide new insight into the role of CDKAL1 in insulin-producing cells and help to understand its involvement in the pathogenesis of diabetes.
None of type 2 diabetes risk alleles at the CDKAL1, CDKN2A/2B, FTO, HHEX-IDE, HMGA2, IGF2BP2, KCNJ11, KCNQ1, MTNR1B, PPARG and SLC30A8 loci were associated with the development of islet autoantibodies or diabetes.
We showed association of the minor allele C of rs10946398 (Odds Ratio (OR) = 1.21, 95% CI = 1.04-1.4, P = 0.016), allele C of rs7754840 (OR = 1.18, 95% CI = 1.01-1.37, P = 0.038), and allele G of rs7756992 (OR = 1.21, 95% CI = 1.04-1.42, P = 0.017) with higher diabetes risk thereby replicating the predisposing role of CDKAL1 in etiology of T2D.
In contrast, variants near insulin-like growth factor-binding protein 2 (IGFBP2), CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1), solute carreir family 30 (zinc transporter), member 8 (SLC30A8), hematopoietically-expressed homeobox (HHEX), and transcription factor 7-like2 (TCF7L2) were clearly associated with diabetes; no evidence for an association to CAC was observable.
Diabetes-associated variants in CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8 and TCF7L2 are associated with physiological alterations leading to T2DM, such as glucose intolerance, impaired insulin secretion or insulin resistance, supporting their role in the disease aetiology.
We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8.