Associations of tumour necrosis factor alpha promoter polymorphisms at position -308 and -238 with clinical characteristics of chronic hepatitis C.
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.
Dai
C-Y
CY
Division of Hepatobiliary, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, No. 100 Tzyou 1st Road, Kaohsiung 807, Taiwan.
Chuang
W-L
WL
Lee
L-P
LP
Chen
S-C
SC
Hou
N-J
NJ
Lin
Z-Y
ZY
Hsieh
M-Y
MY
Hsieh
M-Y
MY
Wang
L-Y
LY
Chang
W-Y
WY
Yu
M-L
ML
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D000483:Alleles; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000276:immunology / Q000821:virology; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase