| Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis |
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| 作者单位： | Hepatic Fibrosis Group,QIMR Berghofer Medical Research Institute, Brisbane 4006,Australia;Faculty of Medicine and Biomedical Sciences,The University of Queensland, Brisbane 4006, Australia;Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital,Brisbane 4029, Australia;Centre for the Advancement of Clinical Research, Royal Brisbane and Women’s Hospital and the University of Queensland Centre for Clinical Research, Brisbane 4029, Australia;Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia;Membrane Transport Laboratory,QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia |
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| 基金项目： | Supported by NHMRC Medical Postgraduate Scholarship and the Royal Brisbane and Women’s Hospital Research Foundation to Wood MJ;the National Health and Medical Research Council(NHMRC)to Ramm GA and Powell LW;the recipient of an NHMRC Senior Research Fellowship,1024672 to Subramaniam VN;an NHMRC Senior Research Fellowship,No.552409 to Ramm GA |
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| 摘 要： | 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-βor TLR4and 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.
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| 关 键 词： | Haemochromatosis Genetic polymorphism Liver fibrosis Toll-like receptor 4 Interleukin 10 Monocyte chemoattractant protein 1 Chemokine(C-C motif) ligand 2 Transforming growth factor beta 8-oxoguanine DNA glycosylase |
| 收稿时间： | 2013-06-12 |
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