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.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of progressive liver disease, which is characterized by obesity, dyslipidemia, type 2 diabetes mellitus (T2DM), hypercholesterolemia, hypertension, insulin resistance, cirrhosis, liver failure and hepatocellular carcinoma [1,2,3]
The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which belong to the nuclear hormone receptor superfamily and Saremi et al Cellular & Molecular Biology Letters (2019) 24:12 consist of three subtypes, each of them encoded by different genes: PPARα (NR1C1), PPARγ (NR1C3) and PPARδ (NP1C2) [3, 16,17,18]
The single nucleotide polymorphisms (SNPs) of the PPAR-γ2 gene have been shown to be associated with susceptibility to several metabolic disorders and many studies have shown a strong relationship between this gene and the occurrence of T2DM in many populations [9, 10, 26, 27]
Summary
Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of progressive liver disease, which is characterized by obesity, dyslipidemia, type 2 diabetes mellitus (T2DM), hypercholesterolemia, hypertension, insulin resistance, cirrhosis, liver failure and hepatocellular carcinoma [1,2,3]. The polymorphism rs1801282 (c.34C > G) on codon 12 of exon B of the PPAR-γ2 gene, which leads to the substitution of proline with alanine (Pro12Ala), was found to be associated with higher insulin sensitivity, lower body mass index (BMI), decreased risk of T2DM and diabetic nephropathy [28,29,30,31,32]. This study aimed to elucidate the association of Pro12Ala with increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus as a common metabolic disorder. Several studies have demonstrated a significant association between Pro12Ala polymorphism of the PPARγ2 gene and metabolic disorders. This study aimed to evaluate the association of Pro12Ala polymorphism with increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus
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