Association of 45-bp ins/del polymorphism of uncoupling protein 2 (UCP2) and susceptibility to nonalcoholic fatty liver and type 2 diabetes mellitus in North-west of Iran

Abstract

Objective Uncoupling protein 2 (UCP2) plays a crucial role in energy homeostasis via insulin secretion regulation, free fatty acid concentrations, and lipid metabolism. This study aimed to investigate the association of 45-bp ins/del polymorphism of UCP2 with susceptibility to NAFLD (Non-Alcoholic Fatty Liver Disease) and T2DM (Type 2 Diabetes Mellitus). DNA was extracted from the white blood cells of the subjects, and the gene polymorphism was determined using polymerase chain reaction (PCR). In this study, 72 patients with NAFLD, 71 healthy individuals as control, 80 patients with T2DM, and 77 healthy controls were enrolled in the study. Results A higher prevalence of insertion/insertion genotype was observed in T2DM patients compared to the controls (p- value˂ 0.05). There was no difference in genotype distribution between NAFLD patients and controls (p-value > 0.05). NAFLD patients with D/D, D/I genotype had higher triglyceride, ALT, and AST levels; however, their HDL levels were lower than healthy controls. Patients with T2DM with D/D or D/I genotype also had significantly higher fasting serum glucose (FSG). While we found an association between the 45 bp I/D polymorphism in 3ʹUTR of UCP2 and T2DM, no correlation between this polymorphism and NAFLD was identified.

Update on Non-Alcoholic Fatty Liver Disease-Associated Single Nucleotide Polymorphisms and Their Involvement in Liver Steatosis, Inflammation, and Fibrosis: A Narrative Review

“…The rs659366 G>A and C>T of the UCP2 gene are correlated with NAFLD susceptibility and fibrosis severity, respectively [ 15 , 71 ] . The carriers of rs659366 A allele are at higher risk of developing NAFLD in Iranian population with NAFLD [ 71 ] .…”

“…The rs659366 G>A and C>T of the UCP2 gene are correlated with NAFLD susceptibility and fibrosis severity, respectively [ 15 , 71 ] . The carriers of rs659366 A allele are at higher risk of developing NAFLD in Iranian population with NAFLD [ 71 ] . The AA genotype shows the high expression of UCP2 and oxidative stress markers, as well as reduced insulin production [ 109 ] .…”

“…J. [41] Significant associations with NAFLD [27] rs2143571 A Significant associations with NAFLD [27] rs2073080 T Significant associations with NAFLD [27] IL-6 rs1800795 C Associated with the development of NASH [64] Higher risk of steatosis with less parenchymal damage [65] Increased risk of NAFLD, higher BMI, fat mass, % body fat, waist circumference, serum TGs, total cholesterol, ALP, AST, and fasting insulin levels [66] rs10499563 C Associated with the presence of definitive NASH, increased ballooning, and Mallory bodies [65] IL-1B rs1143634 T Associated with advanced fibrosis and increased Mallory bodies [65] FNDC5 rs3480 G More severe steatosis [67] AGTR1 rs5186 C Predictor of NAFLD incidence and severity [68] PPARGC1A rs8192678 A Risk factor for the development of NAFLD [69] CD82 rs2303861 G Involved in the development and progression of NAFLD [70] UCP2 rs659366 A Higher risk of NAFLD [71] T Determinant of fibrosis severity [15] TNF-α rs1800629 A Higher risk of NASH development [72] rs1799964 C Independent risk factors contributing to histological progression of NASH [73] NNMT rs694539 A Risk factor for developing NAFLD and NASH, correlated with the steatosis degree [74] HSD11B1 rs2235543 rs12565406 rs4844880…”

Association between UCP2 gene 3’UTR I/D and A55V polymorphisms and neural tube defects susceptibility: systematic review, meta-analysis, and trial sequential analysis

“…While the exact functional implications remained unclear, UCP2 , involved in mitochondrial regulation, might affect bioenergetics and redox balance through specific polymorphisms, influencing NTD development ( 12–14 , 23 ). Polymorphisms might change nutrient availability and interfere with vital pathways in neural tube closure because of the role of UCP2 in energy homeostasis ( 24–28 ). Furthermore, the connection to immunological responses and inflammation, possible interactions with environmental factors, and impact on epigenetic modifications also highlighted how UCP2 was involved in the risk of disease ( 29–31 ).…”

Single-nucleotide polymorphisms as important risk factors of diabetes among Middle East population

“…Uncoupling protein 2 (UCP2) is an anion carrier protein in inner mitochondrial membrane, involved in energy homeostasis, insulin secretion, and metabolism of lipids [ 230 , 231 ]. There was a correlation between UCP2-45 bp I/I polymorphism and increased T2DM risk in a sample of Iranian cases [ 232 ]. NPC1 encodes a protein with vital roles in the intracellular trafficking of sterols.…”