IntroductionTo identify the association of the cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1 (CDKAL1) gene polymorphism with gestational diabetes mellitus (GDM) in the Chinese population.Research design and methodsThis case-control study enrolled 835 pregnant women with GDM and 870 pregnant women without diabetes who underwent antenatal examination during 24 to 28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Trained nurses collected their clinical information and blood samples.CDKAL1gene rs10440833, rs10946398, rs4712523, rs4712524, rs7754840, rs7756992 and rs9465871 loci were genotyped by Agena MassARRAY system. SPSS V.26.0 software and online SHesis were used to analyze the relationship betweenCDKAL1gene polymorphism and GDM susceptibility.ResultsAfter being adjusted for maternal age, prepregnancy body mass index (BMI), parity and family history of type 2 diabetes mellitus (T2DM),CDKAL1gene rs10440833 (AA vs TT, OR=1.631, 95% CI 1.192 to 2.232), rs10946398 (CC vs AA, OR=1.400, 95% CI 1.028 to 1.905), rs4712523(GG vs AA, OR=1.409, 95% CI 1.038 to 1.913), rs4712524 (GG vs AA, OR=1.418, 95% CI 1.043 to 1.929) and rs7754840 (CC vs GG, OR=1.407, 95% CI 1.036 to 1.911) polymorphisms were all associated with the increased risk of GDM. In addition, there was a powerful linkage disequilibrium (LD) among rs10946398, rs4712523, rs4712524 and rs7754840 (D′>0.900, r2>0.900). And there were significant differences in haplotype CGGC (OR=1.207, 95% CI 1.050 to 1.387) and AAAG (OR=0.829, 95% CI 0.721 o 0.952, p=0.008) between the GDM group and the control group.Conclusionsrs10440833, rs10946398, rs4712523, rs4712524 and rs7754840 ofCDKAL1gene are associated with GDM susceptibility in central Chinese population.