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.
Nominal interactions were observed for sleep duration and PPARG rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05).
COL8A1 rs792837 (P=2.9 × 10(-9)), KCNQ1 rs2237892 (P=1.8 × 10(-18)) and rs2237895 (P=0.002), ALX4 rs729287 (Pc=7.5 × 10(-5)), and HNF1 rs4430796 (P=0.003) were significantly associated with T2DM, with similar effect sizes to those of Europeans.
Besides, the haplotype-based analysis demonstrated that AGT in block rs752010-rs4430796-rs7501939 was associated with about 30% increase in T2D risk (OR 1.31, 95% CI 1.09-1.57, P = 0.01).
We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.
Where type 2 diabetes was the outcome, only one statistically significant interaction effect was observed, and this was for the HNF1B rs4430796 variant (P(interaction) = 0.0004).
Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1.16 [95% CI 1.05-1.29], P = 0.0035, empirical P = 0.0475).