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.
Variant of SNP rs10440833 was significantly associated with BMI in T2DM group of both males [OR = 1.8 (1.0, 3.3); P = 0.04] and females [OR = 2.0 (1.0, 3.9); P = 0.04].
We found a significant association of rs7756992, rs7754840 and rs10946398 in CDKAL1 with type 2 diabetes (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.07-1.23, P < 0.0001; OR = 1.14, 95%CI = 1.06-1.24, P = 0.001, and OR = 1.12, 95%CI = 1.07-1.18, P < 0.0001, respectively).
Five risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples.
In Chinese Han, we replicated the associations between 7 genetic loci and T2D, with risk allele-specific odds ratios (ORs) as follows: 1.27 (95% CI, 1.11-1.45; p = 0.0008) for CDKAL1-rs10946398, 1.26 (95% CI, 1.08-1.47; p = 0.003) for IGF2BP2-rs4402960, 1.19 (95% CI, 1.04-1.37; p = 0.009) for SLC30A8-rs13266634, 1.22 (95% CI, 1.06-1.41; p = 0.005) for CDKN2A/B-rs10811661, 1.20 (95% CI, 1.01-1.42; p = 0.03) for HHEX-rs5015480, 1.37 (95% CI, 1.19-1.69; p = 1.0 x 10(-4)) for KCNQ1-rs2237892, and 1.24 (95% CI, 1.01-1.52; p = 0.046) for FTO-rs8050136 after adjustment for age, gender, and body mass index.
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.
In addition, we also confirmed that three SNPs (rs1111875, rs7923837 and rs5015480) in HHEX , one SNP (rs10946398) in CDKAL1, and three SNPs (rs13266634, rs3802177 and rs11558471) in SLC30A8 were significantly associated with T2D in the population being studied.
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.
Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P<or=0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12-1.43) P = 1.8*10(-4); CDKAL1 rs10946398, OR: 1.23 (1.09-1.39); P = 7.1*10(-4), and TCF7L2 rs7903146, OR: 1.61 (1.19-2.18) P = 2.3 * 10(-3).
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.