Genome-Wide Analysis of Copy Number Variation Identifies Candidate Gene Loci Associated with the Progression of Non-Alcoholic Fatty Liver Disease
Genome-Wide Analysis of Copy Number Variation Identifies Candidate Gene Loci Associated with the Progression of Non-Alcoholic Fatty Liver Disease Shamsul Mohd Zain1,2*, Rosmawati Mohamed3*, David N. Cooper4, Rozaimi Razali5, Sanjay Rampal6, Sanjiv Mahadeva3, Wah-Kheong Chan3, Arif Anwar5, Nurul Shielawati Mohamed Rosli5, Anis Shafina Mahfudz7, Phaik-Leng Cheah8, Roma Choudhury Basu9, Zahurin Mohamed1,2 1 The Pharmacogenomics Laboratory, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 2 Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 3 Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 4 Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom, 5 Sengenics Sdn Bhd, High Impact Reseach Building, University of Malaya, Kuala Lumpur, Malaysia, 6 Julius Centre University of Malaya, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 7 Medical Imaging Unit, Faculty of Medicine, University of Technology MARA, Sungai Buloh Campus, Selangor, Malaysia, 8 Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 9 Clinical Investigation Centre, University Malaya Medical Centre, Kuala Lumpur, Malaysia Abstract Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non- alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH.
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