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).


OBJECTIVE
to assess the effect of functional single nucleotide polymorphisms (SNPs) of PPARα and PPARγ2, 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 PPARα and Pro12Ala PPARγ2 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 PPARα 162Val allele (prevalence 57%), but not of the PPARγ2 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 PPARα 162Val and PPARγ2 12Ala alleles were not associated with the severity of steatosis, necroinflammation, or fibrosis.


CONCLUSIONS
The presence of the PPARα 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 PPARγ2 12Ala allele on necroinflammation/fibrosis in NAFLD.
Dongiovanni
Paola
P
Department of Internal Medicine, Metabolic Liver Diseases Research Center, Università degli Studi di Milano, Fondazione Ospedale Policlinico Ca' Granda IRCCS, Milano, Italy.
Rametta
Raffaela
R
Fracanzani
Anna Ludovica
AL
Benedan
Luca
L
Borroni
Vittorio
V
Maggioni
Paolo
P
Maggioni
Marco
M
Fargion
Silvia
S
Valenti
Luca
L
D000483:Alleles; D001706:Biopsy; D015992:Body Mass Index; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D005234:Fatty Liver / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D015995:Prevalence; D012189:Retrospective Studies; D012720:Severity of Illness Index
D047493:PPAR alpha; D047495:PPAR gamma; D004247:DNA
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