Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis

Wood, Marnie J, Powell, Lawrie W, Dixon, Jeannette L, Subramaniam, V. Nathan and Ramm, Grant A (2013) Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis. World Journal of Gastroenterology, 19 48: 9366-9376. doi:10.3748/wjg.v19.i48.9366

Author Wood, Marnie J
Powell, Lawrie W
Dixon, Jeannette L
Subramaniam, V. Nathan
Ramm, Grant A
Title Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis
Journal name World Journal of Gastroenterology   Check publisher's open access policy
ISSN 1007-9327
Publication date 2013-12-28
Year available 2013
Sub-type Article (original research)
DOI 10.3748/wjg.v19.i48.9366
Open Access Status DOI
Volume 19
Issue 48
Start page 9366
End page 9376
Total pages 11
Place of publication Beijing, China
Publisher Beijing Baishideng BioMed Scientific Co
Language eng
Formatted abstract
Aim: To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.

Methods: A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied, with all subjects having liver biopsy data and DNA available for testing. This study assessed the association of eight single nucleotide polymorphisms (SNPs) in a total of six genes including toll-like receptor 4 (TLR4), transforming growth factor-beta (TGF-β), oxoguanine DNA glycosylase, monocyte chemoattractant protein 1, chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity. Genotyping was performed using high resolution melt analysis and sequencing. The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration.

Results: There were significant associations between the cofactors of male gender (P = 0.0001), increasing age (P = 0.006), alcohol consumption (P = 0.0001), steatosis (P = 0.03), hepatic iron concentration (P < 0.0001) and the presence of hepatic fibrosis. Of the candidate gene polymorphisms studied, none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors. We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied. Importantly, in this large, well characterised cohort of patients there was no association between SNPs for TGF-β or TLR4 and the presence of fibrosis, cirrhosis or increasing fibrosis stage in multivariate analysis.

Conclusion: In our large, well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis.
Keyword 8-oxoguanine DNA glycosylase
Chemokine (C-C motif) ligand 2
Genetic polymorphism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
School of Medicine Publications
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