Copy number variation in exportin-4 (XPO4) gene and its association with histological severity of non-alcoholic fatty liver disease

• Published in: Scientific reports Vol. 5; no. 1; p. 13306
• Main Authors: Zain, Shamsul Mohd, Mohamed, Zahurin, Pirmohamed, Munir, Tan, Hwa Li, Alshawsh, Mohammed Abdullah, Mahadeva, Sanjiv, Chan, Wah-Kheong, Mustapha, Nik Raihan Nik, Mohamed, Rosmawati
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.08.2015; Nature Publishing Group
• Subjects: 631/208/457/649/2157; 692/308/2056; Chromosomes, Human, Pair 13 - genetics; Copy number; Demography; DNA Copy Number Variations - genetics; Fatty liver; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genomes; Humanities and Social Sciences; Humans; Karyopherins - blood; Karyopherins - genetics; Liver - pathology; Liver diseases; Male; Middle Aged; multidisciplinary; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - pathology; Science; Severity of Illness Index; Steatosis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep13306

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 (24.6 ng/mL) to simple steatosis (20.8 ng/mL) to NASH (13.8 ng/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.