Mitochondrial uncoupling protein 2 (UCP2) gene polymorphism − 866 G/A in the promoter region is associated with type 2 diabetes mellitus among Kashmiri population of Northern India

• Published in: Molecular biology reports Vol. 50; no. 1; pp. 475 - 483
• Main Authors: Din, Inshah, Majid, Sabhiya, Rashid, Fouzia, Wani, Mumtaz Din, Qadir, Jasiya, Wani, Hilal, Fareed, Mohd
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.01.2023; Springer Nature B.V
• Subjects: Adipose tissue; Age; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; blood serum; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Gene expression; Gene polymorphism; genes; genetic polymorphism; Genotype; Genotyping; heterozygosity; Histology; homozygosity; Humans; India; Insulin; Ion Channels - genetics; Life Sciences; loci; Metabolism; Middle Aged; Mitochondria; Mitochondrial Proteins - genetics; Mitochondrial uncoupling protein 2; Morphology; Mutation; noninsulin-dependent diabetes mellitus; Nucleotide sequence; Original Article; Polymorphism; Polymorphism, Single Nucleotide - genetics; Population studies; promoter regions; Promoter Regions, Genetic; quantitative polymerase chain reaction; risk; Risk factors; Single-nucleotide polymorphism; Uncoupling Protein 2 - genetics; India; Obesity; Kashmiri population; Diabetes; Homozygous mutation; India; UCP2
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-022-08055-z

Objective The study aimed to evaluate the association of UCP2 gene polymorphism − 866 G/A and its expression with diabetes predisposition in the North Indian population. Methods The study involved 850 subjects, including 425 each T2DM and control subjects. The serum metabolic and clinical parameters were estimated using standard protocols. The PCR–RFLP based genotyping was performed to determine UCP2 gene polymorphism, while the expression was measured by real-time quantitative PCR. Results The genotypic and allelic frequencies showed a significant difference in cases compared to controls (p < 0.05). The diabetes patients had a 4.2-fold decrease in UCP2 gene expression. The expression was 29.8 and 8.4 fold lower in diabetes patients with homozygous (AA) and heterozygous (GA) mutation at − 866 locus of UCP2 nucleotide sequence, respectively. When categorized according to age and BMI, the T2DM subjects with age ≥ 50 and BMI ≥ 25 had a 5.53 and 8.2-fold decrease in UCP2 expression, respectively. The diabetes subjects with homozygous and heterozygous mutation demonstrated a pathological increase in serum metabolic and clinical parameters, which corroborated with UCP2 gene expression, indicating a strong association between the two. Intriguingly, we did not find any association between − 866 G/A polymorphism of UCP2 with serum insulin levels. Conclusion Our investigation is the first among the studies conducted in Jammu and Kashmir to work on adipose tissue and UCP2 gene polymorphism. The association of − 866 G/A SNP of the UCP2 gene with its expression in diabetes patients appears to be an important genetic determinant in the progression of T2DM. Moreover, age ≥ 50 years and BMI ≥ 25 could be considered risk factors for developing T2DM in the studied population.