The -866G/A polymorphism in the promoter of the UCP2 gene is associated with risk for type 2 diabetes and with decreased insulin levels

• Published in: Gene Vol. 701; pp. 125 - 130
• Main Authors: Gomathi, Panneerselvam, Samarth, Apurwa P., Raj, Nancy Bright Arul Joseph, Sasikumar, Sundaresan, Murugan, Ponniah Senthil, Nallaperumal, Sivagnanam, Selvam, Govindan Sadasivam
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2019
• Subjects: Insulin; Oxidative stress; Single nucleotide polymorphism; Type 2 diabetes; Uncoupling protein-2; Type 2 diabetes; Oxidative stress; Uncoupling protein-2; FBG; ADP; HDL; SD; DBP; SNP; ANOVA; LDL; VLDL; UCP2; HbA1c; RFLP; BMI; SBP; OR; CI; T2D; IR; Insulin; TC; CVD; DNA; ROS; TGL; HOMA; Single nucleotide polymorphism; ATP; PCR; ELISA
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2019.03.041

Oxidative stress and impaired insulin secretion is an underlying major risk factor for the development of type 2 diabetes (T2D). Uncoupling protein-2 (UCP2) is involved in the regulation of reactive oxygen species production, insulin secretion, and lipid metabolism. Based on this we aimed to find an association of UCP2 (G-866A) polymorphism with the risk of T2D in South Indian population. A total of 318 T2D patients and 312 controls were enrolled in this study. All the study subjects were genotyped for UCP2 (G-866A) polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Fasting blood glucose, HbA1c, serum lipid profile, systolic and diastolic blood pressure were measured by standard biochemical methods. Fasting serum insulin level was measured by ELISA. In UCP2 (G-866A) polymorphism, the distribution of GA (46%) and AA (14%) genotypes were significantly higher in T2D patients than the healthy controls. The frequency of GA and AA genotypes have high risk towards the development of T2D with an Odds Ratio (OR) of 1.55 (P = 0.01) and 2.04 (P = 0.01) respectively. Moreover, SNP-866 G>A allele was found to be significantly associated with T2D (OR = 1.48, P = 0.001, 95% CI = 1.16–1.88). Further, the UCP2 AA genotype showed significantly decreased level of insulin by the reduction in pancreatic β-cell function in T2D patients. UCP2 (G-866A) polymorphism may play a crucial role in the pathogenesis of insulin secretion thus leads to the development of T2D. •UCP2 (G-866A) polymorphism involved in the pathogenesis of type 2 diabetes.•GA and AA genotypes in the promoter region of UCP2 associated with decreased level of insulin in the studied population.•An individual's carrying ‘A’ allele in UCP2 (-866) may require earlier insulin therapy after diagnosis of the disease.•Identification of UCP2 polymorphism could help to early diagnosis of type 2 diabetes.