A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease

Zain, S.M.; Mohamed, R.; Mahadeva, S.; Cheah, P.L.; Rampal, S.; Basu, R.C.; Mohamed, Z. (2012) A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease. Human Genetics, 131 (7).

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    Abstract

    The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurence of fibrosis in patients with NAFLD.

    Item Type: Article
    Creators:
    1. Zain, S.M.
    2. Mohamed, R.
    3. Mahadeva, S.
    4. Cheah, P.L.
    5. Rampal, S.
    6. Basu, R.C.
    7. Mohamed, Z.
    Journal or Publication Title: Human Genetics
    Additional Information: The Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia, soulz712@gmail.com
    Uncontrolled Keywords: Pharmacology
    Subjects: R Medicine
    Divisions: Faculty of Medicine
    Depositing User: Mr. Faizal Hamzah
    Date Deposited: 03 Jul 2012 14:58
    Last Modified: 11 Dec 2013 10:31
    URI: http://eprints.um.edu.my/id/eprint/3462

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