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Gene variants linked to steatosis, fibrosis, steatohepatitis
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Variants in the PNPLA3, GCKR, TRIB1 and PPP1R3B genes are associated with histological factors of nonalcoholic fatty liver disease, according to data presented at the International Liver Congress in Amsterdam.
Researchers assessed genetic variation among 1,125 Caucasian patients with nonalcoholic fatty liver disease (NAFLD) from North America and Europe. These patients were participants in a recent genome-wide association study. Data on six genes (PNPLA3, NCAN, LYPLAL1, GCKR and PPP1R3B) linked in prior studies to NAFLD and one, TRIB1, previously linked to persistent ALT elevation, were collected and compared with that of 6,000 controls.
Multivariate analysis indicated significant associations between four gene variants (PNPLA3 rs738409, GCKR rs780094, TRIB1 rs2385114 and PPP1R3B rs11777327) and steatosis after adjustment for factors including age, BMI, diabetes and insulin resistance. PNPLA3, GCKR and TRIB1 variants also were significantly associated with fibrosis and steatohepatitis. No associations were observed between NAFLD and either NCAN or LYPLAL1.
“This candidate-gene study across the histological spectrum of NAFLD has further established the overwhelming significance of the chromosome 22 PNPLA3 locus to all aspects of NAFLD and has, for the first time, demonstrated that variations in some loci previously associated with steatosis or mild biochemical abnormalities may have broader pathological significance influencing inflammatory disease and progression to fibrosis in NAFLD,” the researchers concluded.
For more information:
Anstee QM. #104: A Candidate-Gene Approach to Validation of Genetic Modifier Associations Using a Large Cohort With Histologically Characterized Nonalcoholic Fatty Liver Disease. Presented at: The International Liver Congress 2013; April 24-28, Amsterdam.