Lack of association between peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms and progressive liver damage in patients with non-alcoholic fatty liver disease: a case control study

Background: Peroxisome proliferator-activated receptors (PPARs) play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Aim: to assess the effect of functional single nucleotide polymorphisms (SNPs) of PPAR alpha and PPAR gamma 2, previously associated with insulin resistance and dyslipidemia, on liver damage in NAFLD, whose progression is influenced by metabolic abnormalities and inherited factors. Methods: The Leu162Val PPAR alpha and Pro12Ala PPAR gamma 2 SNPs were evaluated by restriction analysis. We considered 202 Italian patients with biopsy-proven NAFLD. Results: The frequency of the evaluated SNPs did not differ between patients and 346 healthy controls. The presence of the PPAR alpha 162Val allele (prevalence 57%), but not of the PPAR gamma 2 12Ala allele (prevalence 18%), was associated with higher insulin resistance (HOMA-IR index 4.71 +/- 3.8 vs. 3.58 +/- 2.7, p = 0.026), but not with hyperglycemia. The PPAR alpha 162Val and PPAR gamma 2 12Ala alleles were not associated with the severity of steatosis, necroinflammation, or fibrosis. Conclusions: The presence of the PPAR alpha 162Val allele was associated with insulin resistance, but not with liver damage in NAFLD. Because of the limited power of the present sample, larger studies are needed to exclude a minor effect of the PPAR gamma 2 12Ala allele on necroinflammation/fibrosis in NAFLD.