Association of CDKAL1 gene polymorphisms with type 2 diabetes mellitus in a sample of Iraqi population

Abstract

BackgroundType 2 Diabetes Mellitus (T2DM) is a multifactorial disorder in which genetic in addition to environmental factors such as excess carbohydrate intake and sedentary lifestyle play crucial role in the pathogenesis. Genome-wide association study (GWAS) identified many genes that impact on pathogenesis of T2DM, also the role of these genes in complications of diabetes and glucose homeostasis. MethodsA case-control study consisted of 400 T2DM patients and 400 control was conducted. Phenotyping and anthropometric data included body mass index (BMI), fasting plasma glucose (FPG), lipid profile and insulin levels applied for two groups. Genotyping of CDKAL1 gene single-nucleotide polymorphisms (SNPs) (rs7754840 G>C and rs7756992 A>G) polymorphisms were carried out using PCR-RFLP. ResultsThe results of CDKAL1 gene rs7754840 SNP in T2DM and control persons under the co-dominant model revealed that T2DM patients with the heterozygous genotype (GC) (OR = 1.93, CI 95%; 1.32–2.34, P < 0.0001) and homozygous genotype (GG) (OR = 3.44, CI 95%; 1.36–6.39, P = 0.009) illustrates profound association between T2DM and the investigated SNP. The minor allele frequency (C) was elucidated to be significantly (OR = 2.03, CI95% = 1.57–2.61, P = 0.0001) increased in T2DM patients (25.1%) in relation to control group (14.25%). Odds ratio was adjusted for BMI, age and gender and this not affect the results. ANOVA test for mean comparison of biochemical markers under the co-dominant model of rs7754840 SNP genotype in CDKAL1 gene, revealed a significant difference for insulin (P < 0.0001) and HOMA-IR (P < 0.0001). Genotyping results of CDKAL1 gene (rs7756992) SNP did not show any significant association between T2DM and control group. ConclusionThe results of this study revealed an association between CDKAL1 (rs7754840) gene polymorphism with T2DM in a sample of Iraqi population, furthermore this SNP significantly affect insulin level in those patients. While CDKAL1 (rs7756992) gene polymorphism did not show any significance.