In patients, increased expression of CDK5 tv2, CDKN2A tv3 or THADA tv5 correlated positively with serum insulin levels, of CDK5 tv1 positively with % HbA1c levels, while in controls, elevated levels of TSPAN8 were associated positively with the presence of T2D family history.
The results of this study indicate that the use of 8 genetic polymorphisms associated with carbohydrate and lipid metabolism and type 2 diabetes [<i>PTGS2</i> (<i>COX2</i>) rs6681231, <i>FADS1</i> rs174550, <i>HNF1B</i> rs4430796, <i>ADIPOQ</i> rs266729, <i>IL18</i> rs187238, <i>CCL2</i> rs1024611, <i>HHEX</i> rs5015480 and <i>CDKN2A/2B</i> rs10811661] together with clinical risk factors (BMI and age) may significantly improve the prediction of GDM.
Reduced mRNA levels of CDKN2A (p16<sup>Ink4a</sup>), CDKN2B (p15<sup>Ink4b</sup>), and CDKN2BAS were observed in human T2DM and T2DM-CAD subjects compared with controls.
The goal of this study was to determine whether <i>CDKN2A/B</i> T2D risk SNPs impact locus gene expression, insulin secretion, or β-cell proliferation in human islets.
Genome-wide association studies have reported that DNA polymorphisms at the CDKN2A locus modulate fasting glucose in human and contribute to type 2 diabetes (T2D) risk.
To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent.
There were potential interactions among CDKN2A/2B (rs10811661) - FTO (rs7195539) or FTO (rs7195539)-TG-HDL-family history of diabetes in the pathogenesis of T2D in a Uyghur population.
Overall, we demonstrated that CDKN2A is an important regulator of glucose homeostasis in humans, thus supporting its candidacy as an effector transcript for type 2 diabetes-associated alleles in the region.
Using this approach, numerous studies have associated SNPs on chromosome 9p21.3 situated near the cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) locus with the risk for coronary artery disease (CAD) and T2D.
Thus, we aimed to investigate the contribution of rs1111875 (HHEX), rs1800961 (HNF4α), rs5219 (KCNJ11), rs1801282 (PPARγ), rs10811661 (CDKN2A/2B), rs13266634 (SLC30A8), rs12779790 (CDC123/CAMK1D), rs7903146 (TCF7L2), rs9282541 (ABCA1) and rs13342692 (SLC16A11) polymorphisms in the genetic background of Maya population to associate their susceptibility to develop T2D.
For example, the most significant SNP, rs10811661 near CDKN2A/2B (P = 1.11×10(-8) for T2D), was also associated with 2-h glucose level of an oral glucose tolerance test (P = 9.11×10(-3)) and insulinogenic index (P = 2.71×10(-2)).
Furthermore, a two-factor gene-environment interaction model of CDKN2A/B (rs10757274) and type 2 diabetes mellitus (T2DM) was identified to be the best model by GMDR (p = 0.0107), with a maximum prediction accuracy of 59.18%, and a maximum Cross-validation Consistency of 10/10.
We have shown for the first time that variants at WFS1, JAZF1, SLC30A8, CDKN2A/B, TCF7L2, KCNQ1, HMG20A, HNF4A and DUSP9 are associated with T2D in the Saudi population.
The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA.