Association of CDKN2A/B gene polymorphisms (rs10811661 and rs2383208) with type 2 diabetes mellitus in a sample of Iraqi population

Abstract

Background Type 2 diabetes mellitus (T2DM) is chronic metabolic disorder manifested by increased blood glucose (hyperglycemia) due to pancreatic β-cell dysfunction and/or decreased sensitivity of peripheral tissue to insulin. T2DM is a multifactorial disease that may results from interaction of environmental and genetic factors. Methods A case–control study consisting of 400 T2DM patients in addition to 400 as control. Phenotyping as well as anthropometric data included body mass index BMI, fasting plasma glucose (FPG), serum total cholesterol, serum triglyceride, VLDL, LDL, HDL insulin levels and Homeostatic Model Assessment for Insulin Resistance HOMA-IR were estimated for the two groups. PCR–RFLP was used to carry out genotyping of CDKN2A/B gene (rs10811661 T>C and rs2383208 A>G) SNPs. Results For rs10811661 SNP the genotype and allele frequencies of CDKN2A/B gene for T2DM and control subjects showed that the co-dominant model in patients with the homozygous (TT) was found to be significantly (OR 2.51, 95% CI 1.47–4.24, P 0.004) higher than those in control group. In contrast, the heterozygous genotype (TC) did not reveal this significance (OR 1.14, 95% CI 0.77–2.62, P = 0.13), ANOVA test for mean comparison of biochemical markers under the co-dominant model of rs10811661 SNP genotype in CDKN2A/B gene, revealed a significant difference for insulin (P < 0.0001) and HOMA-IR (P < 0.0001) in T2DM group as compared to control one; However (rs2383208) SNP did not show any significant association with T2DM and with the measured biochemical marker at any model. Conclusions CDKN2A/B gene rs10811661 SNP was implicated in T2DM pathogenesis in this sample of Iraqi population also it affects insulin level in those patients, whereas the rs2383208 SNP did not impact the disease.

Association of Polygenic Variants with Type 2 Diabetes Risk and Their Interaction with Lifestyles in Asians

“…Its variants also affect insulin response in persons of European ancestry [ 45 ]. CDKN2A/B locus encodes p15 and p16 inhibitors for cyclin-dependent kinase 4 ( CDK4 ), which regulates pancreatic β-cell replication [ 46 ]. The increased expression of CDKN2B induces hypoplasia of the exocrine and endocrine glands in rodents, and CDK4 inhibition induces insulin deficiency due to decreased pancreatic β-cell counts [ 46 ].…”

“…CDKN2A/B locus encodes p15 and p16 inhibitors for cyclin-dependent kinase 4 ( CDK4 ), which regulates pancreatic β-cell replication [ 46 ]. The increased expression of CDKN2B induces hypoplasia of the exocrine and endocrine glands in rodents, and CDK4 inhibition induces insulin deficiency due to decreased pancreatic β-cell counts [ 46 ]. CDKN2A/B _rs10811661 carriers are susceptible to T2DM risk in different ethnic groups, including the Iraqi, Chinese, and Tai populations [ 46 , 47 , 48 ].…”

“…The increased expression of CDKN2B induces hypoplasia of the exocrine and endocrine glands in rodents, and CDK4 inhibition induces insulin deficiency due to decreased pancreatic β-cell counts [ 46 ]. CDKN2A/B _rs10811661 carriers are susceptible to T2DM risk in different ethnic groups, including the Iraqi, Chinese, and Tai populations [ 46 , 47 , 48 ]. Consistent with the present study results, Asians carrying CDKAL1 _rs35612982, CDKN2A/B _rs10811661, and KCNQ1 _rs60808706, which are mainly linked to β-cell mass, have an elevated susceptibility to T2DM, suggesting that T2DM in Asians may be closely related to reduced β-cell mass and function.…”

Integration of omics technologies for the identification of predictive biomarkers in type 2 diabetes: a comprehensive analysis of recent literature

“…Consequently, genes like, CDKAL1, KCNQ1, and CDKN2A/B, have been strongly associated with T2DM. Their SNPs have been found in blood, as well as in tissue of diabetic targets, linking them with possible blood-based biomarkers for these different types of diabetes (Fadheel et al, 2022).…”