The Pro12Ala polymorphism in the PPAR­γ2 gene is not associated with an increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus

Abstract

BackgroundThe peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. Several studies have demonstrated a significant association between Pro12Ala polymorphism of the PPAR­γ2 gene and metabolic disorders. Therefore, this study aimed to evaluate the association of Pro12Ala polymorphism with increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus.MethodsThis cross-sectional study was performed on 145 healthy control subjects and 145 NAFLD patients with a history of type 2 diabetes. Pro12Ala polymorphism genotyping was performed using PCR–restriction fragment length polymorphism (RFLP) technique with the Bs1I restriction enzyme.ResultsOur results demonstrated that CC and GG genotypes of Pro12Ala were found in the participants, but there was no statistically significant difference between NAFLD patients and healthy controls (P = 0.64 and χ2 = 0.21).ConclusionThis study suggests that Pro12Ala polymorphism of the PPAR­γ2 gene cannot be considered as a risk factor for NAFLD in the Iranian population.

Association between PPARGC1A single nucleotide polymorphisms and increased risk of nonalcoholic fatty liver disease among Iranian patients with type 2 diabetes mellitus

“…Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disorder in developed countries, and it affects more than 70% of patients with type 2 diabetes mellitus and people suffering from obesity [1,2]. NAFLD is characterized by hepatic and systemic insulin resistance, dyslipidemia, and persistent abnormalities in the liver enzymes [3][4][5]. NAFLD comprises a broad spectrum of disease severity, ranging from benign hepatocellular steatosis to nonalcoholic steatohepatitis (NASH-fatty changes with inflammation and hepatocellular damages), advanced liver cirrhosis, hepatocellular carcinoma, and increased risk of liver-related mortalities [6].…”

<p>Type 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors</p>

“…PPARγ2 (peroxisome proliferator-activated receptorgamma 2) is a ligand-activated transcription factor of the nuclear hormone receptor superfamily. 187 The PPARγ2 gene plays roles in glucose homeostasis, lipid metabolism, obesity, insulin sensitivity, T2DM, and various adipocytespecific genes. 59,[188][189][190] Based on several case-control and family-based studies, estimated that Pro12 allele (ie, the major allele) of PPARγ was associated with a 1.25-fold elevated risk of T2DM.…”

Molecular Dynamics Simulation and Essential Dynamics of Deleterious Proline 12 Alanine Single-Nucleotide Polymorphism in PPARγ2 Associated with Type 2 Diabetes, Cardiovascular Disease, and Nonalcoholic Fatty Liver Disease

“…Increasing experimental studies have investigated the relationship between Pro12Ala polymorphism of PPARγ2 gene and various diseases such as T2DM, insulin sensitivity, obesity, cardiovascular diseases, Alzheimer's disease, and cancer [ 3 ]. Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that is determined by dyslipidemia, obesity, hypertension, hypercholesterolemia, type 2 diabetes mellitus, cirrhosis, liver failure, insulin resistance, and hepatocellular carcinoma [ 9 ]. Several researchers reported that Pro12Ala polymorphism was significantly associated with NAFLD [ 10 – 13 ] in different populations.…”

“…Different studies have also shown which PPAR γ 2 Pro12Ala polymorphism was associated with CAD [ 8 , 14 ]. Saremi et al found PPAR γ 2 (c.34G>C, Pro12Ala) is considerably associated with higher risk NAFLD [ 9 ] in T2DM patients in Iranian population. These findings suggest a high possibility of involvement of Pro12Ala polymorphism in the risk for CAD, NAFLD, and T2DM.…”