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Associations of tumour necrosis factor alpha promoter polymorphisms at position −308 and −238 with clinical characteristics of chronic hepatitis C
Author(s) -
Dai CY.,
Chuang WL.,
Lee LP.,
Chen SC.,
Hou NJ.,
Lin ZY.,
Hsieh MY.,
Hsieh MY.,
Wang LY.,
Chang WY.,
Yu ML.
Publication year - 2006
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2006.00767.x
Subject(s) - genotype , hepatitis c virus , allele , promoter , restriction fragment length polymorphism , medicine , hepatitis c , gastroenterology , allele frequency , odds ratio , fibrosis , tumor necrosis factor alpha , biology , microbiology and biotechnology , immunology , gene , virus , gene expression , genetics
Summary. The aim of this study was to investigate the association between G vs A transitions in the promoter region of the tumour necrosis factor (TNF) alpha at positions −308 (TNF308.2) and −238 (TNF238.2) and clinical features of chronic hepatitis C (CHC). These two promoter TNF‐alpha variants were determined in 250 biopsy‐proven CHC patients by polymerase chain reaction amplification, followed by the Restriction Fragment Length Polymorphism (RFLP) method. The distribution of −308 and −238 TNF‐alpha promoter genotypes were TNF308.1/TNF308.1: 187 (74.8%), TNF308.1/TNF308.2: 57 (22.8%) and TNF308.2/TNF308.2: 6 (2.4%), respectively, and TNF238.1/TNF238.1: 247 (98.8%) and TNF238.1/TNF238.2: 3 (1.2%). The frequencies of the TNF308.2 and TNF238.2 promoter alleles were 13.8% and 0.6%. Increased TNF308.2 allele copy numbers were significantly associated with increased frequency of lower pretreatment hepatitis C virus (HCV) RNA levels (<800 000 IU/mL; P = 0.031) and severe fibrosis stage (F3‐F4; P = 0.006) and higher mean fibrosis score ( P = 0.007). The higher cytokine production (with one or two TNF308.2 alleles) was correlated significantly with lower pretreatment HCV RNA levels with a lower mean HCV RNA level ( P = 0.024) and increased frequency of lower pretreatment HCV RNA levels (<800 000 IU/mL; P = 0.017). Stepwise logistic regression showed that higher fibrosis score and low HCV RNA levels were independently related to the TNF308.2 allele [odds ratio (95% CI): 1.385 (1.127–1.702) and 0.698 (0.488–0.990)]. We conclude that inheritance of the TNF‐alpha promoter genotype at the position −308 appears to be associated with variability in severity of fibrosis and viral load in chronic HCV infection.