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PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease
Author(s) -
Speliotes Elizabeth K.,
Butler Johannah L.,
Palmer Cameron D.,
Voight Benjamin F.,
Hirschhorn Joel N.
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23768
Subject(s) - nonalcoholic fatty liver disease , single nucleotide polymorphism , odds ratio , medicine , steatosis , fatty liver , gastroenterology , allele , metabolic syndrome , biology , endocrinology , pathology , disease , genetics , genotype , obesity , gene
Single nucleotide polymorphisms (SNPs) near 7 loci have been associated with liver function tests or with liver steatosis by magnetic resonance spectroscopy. In this study we aim to test whether these SNPs influence the risk of histologically‐confirmed nonalcoholic fatty liver disease (NAFLD). We tested the association of histologic NAFLD with SNPs at 7 loci in 592 cases of European ancestry from the Nonalcoholic Steatohepatitis Clinical Research Network and 1405 ancestry‐matched controls. The G allele of rs738409 in PNPLA3 was associated with increased odds of histologic NAFLD (odds ratio [OR] = 3.26, 95% confidence intervals [CI] = 2.11‐7.21; P = 3.6 × 10 −43 ). In a case only analysis of G allele of rs738409 in PNPLA3 was associated with a decreased risk of zone 3 centered steatosis (OR = 0.46, 95% CI = 0.36‐0.58; P = 5.15 × 10 −11 ). We did not observe any association of this variant with body mass index, triglyceride levels, high‐ and low‐density lipoprotein levels, or diabetes ( P > 0.05). None of the variants at the other 6 loci were associated with NAFLD. Conclusion: Genetic variation at PNPLA3 confers a markedly increased risk of increasingly severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits. (H EPATOLOGY 2010)