Genome-wide analysis of copy number variation identifies candidate gene loci associated with the progression of non-alcoholic fatty liver disease

Shamsul Mohd Zain, Rosmawati Mohamed, David N. Cooper, Rozaimi Mohamad Razali, Sanjay Rampal, Sanjiv Mahadeva, Wah Kheong Chan, Arif Anwar, Nurul Shielawati Mohamed Rosli, Anis Shafina Mahfudz, Phaik Leng Cheah, Roma Choudhury Basu, Zahurin Mohamed

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 nonalcoholic 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. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in 'second hit' hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH.

Original languageEnglish
Article numbere95604
JournalPLoS One
Volume9
Issue number4
DOIs
Publication statusPublished - 17 Apr 2014
Externally publishedYes

Fingerprint

fatty liver
Liver
Genes
Genome
loci
genome
liver cirrhosis
genes
hepatoma
disease course
pathogenesis
comparative genomic hybridization
Karyopherins
Type 4 Cyclic Nucleotide Phosphodiesterase
Disease Progression
Hepatocellular Carcinoma
Cell death
Microarrays
Ports and harbors
etiology

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Genome-wide analysis of copy number variation identifies candidate gene loci associated with the progression of non-alcoholic fatty liver disease. / Zain, Shamsul Mohd; Mohamed, Rosmawati; Cooper, David N.; Mohamad Razali, Rozaimi; Rampal, Sanjay; Mahadeva, Sanjiv; Chan, Wah Kheong; Anwar, Arif; Rosli, Nurul Shielawati Mohamed; Mahfudz, Anis Shafina; Cheah, Phaik Leng; Basu, Roma Choudhury; Mohamed, Zahurin.

In: PLoS One, Vol. 9, No. 4, e95604, 17.04.2014.

Research output: Contribution to journalArticle

Zain, SM, Mohamed, R, Cooper, DN, Mohamad Razali, R, Rampal, S, Mahadeva, S, Chan, WK, Anwar, A, Rosli, NSM, Mahfudz, AS, Cheah, PL, Basu, RC & Mohamed, Z 2014, 'Genome-wide analysis of copy number variation identifies candidate gene loci associated with the progression of non-alcoholic fatty liver disease', PLoS One, vol. 9, no. 4, e95604. https://doi.org/10.1371/journal.pone.0095604
Zain, Shamsul Mohd ; Mohamed, Rosmawati ; Cooper, David N. ; Mohamad Razali, Rozaimi ; Rampal, Sanjay ; Mahadeva, Sanjiv ; Chan, Wah Kheong ; Anwar, Arif ; Rosli, Nurul Shielawati Mohamed ; Mahfudz, Anis Shafina ; Cheah, Phaik Leng ; Basu, Roma Choudhury ; Mohamed, Zahurin. / Genome-wide analysis of copy number variation identifies candidate gene loci associated with the progression of non-alcoholic fatty liver disease. In: PLoS One. 2014 ; Vol. 9, No. 4.
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