We found a significant association between CDKAL1 polymorphisms (rs4712523, OR 1.42, p = 9.44 × 10-5; rs4712524, OR 1.38, p = 3.28 × 10-4; rs10946398, OR 1.43, p = 6.21 × 10-5; rs7754840, OR 1.43, p = 6.33 × 10-5; rs35612982, OR 1.34, p = 0.0010; and rs10440833, OR 1.32, p = 0.0018) and T2D risk among the Han population from Northwest China.
We found a significant association between CDKAL1 polymorphisms (rs4712523, OR 1.42, p = 9.44 × 10-5; rs4712524, OR 1.38, p = 3.28 × 10-4; rs10946398, OR 1.43, p = 6.21 × 10-5; rs7754840, OR 1.43, p = 6.33 × 10-5; rs35612982, OR 1.34, p = 0.0010; and rs10440833, OR 1.32, p = 0.0018) and T2D risk among the Han population from Northwest China.
HbA1c reduction after use of DPP-4 inhibitors for 3 months was significantly greater in patients with a risk allele for type 2 diabetes (GG -0.4%, CG -0.5%, CC -0.8%, p = 0.02 for rs7754840 and AA -0.4%, AG -0.5%, GG -0.8%, p = 0.01 for rs7756992).
HbA1c reduction after use of DPP-4 inhibitors for 3 months was significantly greater in patients with a risk allele for type 2 diabetes (GG -0.4%, CG -0.5%, CC -0.8%, p = 0.02 for rs7754840 and AA -0.4%, AG -0.5%, GG -0.8%, p = 0.01 for rs7756992).
Cyclin- dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1) rs10946398, a novel body mass index (BMI)-associated locus specifically in the Asian population, may impair insulin secretion and may be associated with insulin resistance and type 2 diabetes.
We found a lower risk of prediabetes and type 2 diabetes combined with coffee intake among individuals with the GT/TT of IGF2BP2 rs4402960, GG/GC of CDKAL1 rs7754840, or CC of KCNJ11 rs5215, which are known to be related to type 2 diabetes in East Asians.
In this study, we investigated the association of the rs7756992 of CDKAL1 and the rs4402960 of IGF2BP2 with Type 2 diabetes, diabetic complications (nephropathy, retinopathy and cardiovascular disease), obesity and hypertension in a Tunisian population.
In a simple linear regression model, expression of CDKAL1-v1 was associated with the lead type 2 diabetes-associated SNP, rs7756992, in whole blood and islets.
Five risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples.
Associations with type 2 diabetes mellitus have been identified for variants CDKAL1 rs7756992, KCNJ11 rs5219, and IGF2BP2 rs4402960 in different populations.
Taken together, our findings provide evidence for a significant contribution of CDKN2A/B gene rs10811661 and CDKAL1 gene rs7756992 and rs10946398 to type 2 diabetes.
Meanwhile PPARG-2 Pro12Ala, CDKN2A/2B rs10811661, IGF2BP2 rs4402960, HHEX rs7923837, CDKAL1 rs7754840, EXT2 rs1113132 and SLC30A8 rs13266634 were found to have no significant association with T2D among Arabs.
In meta-regression analyses, age was found to exert a significant influence on the association between rs10811661 and type 2 diabetes (P=0.003), as well as between rs7754840 and gender (P=0.034).
In the whole population, a significant association was found between CDKAL1 gene rs7756992A/G polymorphism and T2DM under allelic (OR: 1.180, 95% CI: 1.130-1.230, P = 1.60 × 10⁻¹⁴), recessive (OR: 1.510, 95% CI: 1.380-1.660, P = 8.41 × 10⁻¹⁸), dominant (OR: 1.175, 95% CI: 1.109-1.246, P = 6.30 × 10⁻⁸), homozygous (OR: 1.400, 95% CI: 1.282-1.530, P = 8.02 × 10⁻¹⁴), and heterozygous genetic models (OR: 1.101, 95% CI: 1.040-1.166, P = 0.001).
Taken together, our findings provide evidence for a significant contribution of CDKN2A/B gene rs10811661 and CDKAL1 gene rs7756992 and rs10946398 to type 2 diabetes.
In addition, rs7754840 (CDKAL1) was associated in the nonobese type 2 diabetic subgroup, and for rs7903146 (TCF7L2), association was observed for early-onset type 2 diabetes.
Two loci known to be associated with type 2 diabetes had a genome-wide significant association with GDM in the joint analysis. rs7754840, a variant in CDKAL1, had the strongest association with GDM (odds ratio 1.518; P=6.65×10(-16)).