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.
ABSTRACT. We integrated all the eligible studies and investigated whether the TNF-α 308G/A polymorphism correlates with urogenital cancer risk. Tumor necrosis factor-α (TNF-α) is a risk factor for some urogenital cancers; however, in prostate and bladder cancers the results are controversial. PubMed, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, and the Wanfang Database were searched for all case-control studies on the relationship between the TNF-α 308G/A polymorphism and susceptibility to urogenital cancer between January 1994 and January 2015. The pooled odds ratio with 95% confidence interval was calculated to assess the associations. A total of 16103 Association between TNF-α 308G/A and urogenital cancer risk ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16102-16112 (2015) 504 articles were found, 39 of which involved 11,613 cases and 12,542 controls that fulfilled the inclusion criteria. Overall, the TNF-α 308G/A polymorphism was significantly associated with the risk of urogenital cancer. In the subgroup analysis for different cancer types, significant associations were found in cervical cancer and urothelial carcinoma, while our metaanalysis indicated that there were no significant associations between the TNF-α 308G/A polymorphism and prostate, bladder, or renal cancers. When stratified by ethnicity, significant associations were observed in Caucasian populations, whereas no significant associations were found in African-Americans, Asians, or mixed populations. Furthermore, carriers of the -308A allele among the hospital-based case-control group were at a high risk of urogenital cancer. Our meta-analysis showed that the TNF-α 308G/A polymorphism was significantly associated with urogenital cancer risk, particularly in the Caucasian and hospital-based populations.
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