| ObjectiveTo explore the associations between rs4712523,rs7754840 and rs7756992polymorphisms of Cyclin-dependent kinase 5 regulatory subunit associated protein 1like 1(CDKAL1)gene and type 2 diabetes mellitus(T2DM)and diabetes-related traits.MethodsA total of 527 T2DM cases were randomly selected from the Henan Rural CohortStudy(Registration number:ChiCTR-OOC-15006699).The 527 controls were matched based on the same sex and age±3 years in the same cohort population.The Genomic DNA was extracted from the whole blood using Whole Blood Genomic DNA Medium extraction kit III(Magnetic bead).A custom-by-design 2×48-Plex SNPscanTM Kit was used to detect the genotypes.χ~2 test and signed-rank test were used to compare the significance of difference of categorical variables and continuous variables,respectively.Kruskal-Wallis H test was performed to explore the distribution differences of diabetes-related traits under different genotypes,and Spearman rank correlation was used to explore the correlation between SNPs and diabetes-related traits.Conditional logistic regression was used to investigate the associations of three SNPs with T2DM susceptibility in different genetic models.The simple genetic risk score(GRS)and weighted GRS were concluted.Spearman rank correlation was used to explore the correlation between GRSs and diabetes-related traits,and conditional logistic regression was performed to assess the associations of GRSs with T2DM.Generalized multifactor dimensionality reduction method was used to test the interaction between gene and environmental factors.Haplotype analysis of three SNPs of the CDKAL1 gene was performed by R software’s Haplo.stats software package.Results1.Compared with the controls,the cases had more people with low physical activity and fewer people with high physical activity,and had a higher family history of diabetes,systolic blood pressure,diastolic blood pressure,pulse pressure,heart rate,waist circumference,hip circumference,body mass index(BMI),total cholesterol(TC),triglyceride(TG),fasting plasma glucose(FPG)and fasting insulin(FINS)concentrations,lower high density lipoprotein cholesterol(HDL-C)concentrations.2.There was no significant difference in the genotype distributions of rs4712523,rs7754840 and rs7756992 in case and control groups(P>0.05),and the distributions in the control group according with the Hardy-Weinberg equilibrium(P>0.1).3.The significant correlations between rs4712523,rs7754840 and rs7756992polymorphisms and FPG(rs(P)were 0.097(0.002),0.092(0.003)and 0.081(0.009),respectively)and homeostasis model assessment ofβ-cell function(HOMA-β)(r_s(P)were-0.087(0.005),-0.093(0.003)and-0.071(0.022),respectively)were observed in total population.No significant correlation of the polymorphisms with FINS and homeostasis model assessment of insulin resistance(HOMA-IR)were noted.4.No significant association of the polymorphisms with T2DM was detected in different genetic models.5.The significant correlations between simple and weight GRS and FPG(r_s(P)were 0.093(0.002)and 0.094(0.002),respectively)and HOMA-β(rs(P)were-0.087(0.005)and-0.089(0.004),respectively)were only observed in total population,and no significant correlation of the GRSs with FINS and HOMA-IR were found.6.There was no statistical association between haplotypes of CDKAL1 and T2DM(P>0.05),and no significant interaction between CDKAL1 gene and environmental factors on T2DM.Conclusion1.The SNPs of rs4712523,rs7754840 and rs7756992 were associatied with FPG and HOMA-β.The accumulation of mutant alleles in CDKAL1 gene could decrease the function of isletβcell and increase the concentration of FPG.2.There was no significant association between rs4712523,rs7754840 and rs7756992 polymorphisms of CDKAL1 gene and T2DM.3.No significant association between haplotypes of CDKAL1 gene and T2DM,and interaction effect between the CDKAL1 gene and environmental factors was found. |
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