Zain, Shamsul Mohd and Mohamed, Zahurin and Pirmohamed, M. and Tan, H.L. and Alshawsh, Mohammed Abdullah and Mahadeva, Sanjiv and Chan, Wah Kheong and Mustapha, N.R.N. and Mohamed, Rosmawati (2015) Copy number variation in exportin-4 (XPO4) gene and its association with histological severity of non-alcoholic fatty liver disease. Scientific Reports, 5 (1). p. 13306. ISSN 2045-2322, DOI https://doi.org/10.1038/srep13306.
Full text not available from this repository.Abstract
A recent genome-wide copy number (CNV) scan identified a 13q12.11 duplication in the exportin-4 (XPO4) gene to be associated with non-alcoholic steatohepatitis (NASH). We sought to confirm the finding in a larger cohort and to assess the serum XPO4 pattern in a broad spectrum of non-alcoholic fatty liver disease (NAFLD) cases. We analysed 249 NAFLD patients and 232 matched controls using TaqMan assay and serum XPO4 was measured. Copy number distribution was as follows: copy number neutral (NAFLD: 53.8%, controls: 68.6%), copy number losses (NAFLD: 13.3%, controls: 12.9%), copy number gains (NAFLD: 32.9%, controls: 18.5%). CNV gain was significantly associated with a greater risk of NAFLD (adjusted OR 2.22, 95% CI 1.42-3.46, P=0.0004) and NASH (adjusted OR 2.33, 95% CI 1.47-3.68, P=0.0003). Interestingly, subjects carrying extra copy number showed significantly higher serum ALT and triglyceride (P<0.05). Serum XPO4 levels progressively declined (P=0.043) from controls (24.6ng/mL) to simple steatosis (20.8ng/mL) to NASH (13.8ng/mL). In conclusion, XPO4 CNV duplication was associated with histological severity of NAFLD, and accompanied by changes in serum XPO4 levels providing insights into NAFLD pathogenesis, and has the potential for biomarker development.
| Item Type: | Article |
|---|---|
| Funders: | UNSPECIFIED |
| Uncontrolled Keywords: | Chromosomes, Human, Pair 13; Demography; DNA Copy Number Variations; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Karyopherins; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Severity of Illness Index |
| Subjects: | R Medicine R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 19 Sep 2018 05:20 |
| Last Modified: | 25 Oct 2019 09:22 |
| URI: | http://eprints.um.edu.my/id/eprint/19296 |
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