Background: Tumor necrosis factor alpha (TNF-á) has been involved in the pathogenesis of chronic hepatitis C virus (HCV) infection. Two polymorphisms at positions -308 and -238 in the TNF-á promoter region influence TNF-á expression and these have been linked to a number of infectious diseases. Aim: To analyze the prevalence of the -308 and -238 TNF-á polymorphisms in a group of Mexican HCV-infected patients and in healthy control subjects not related to the patients. Material and methods: Both polymorphisms were determined in peripheral blood samples from 48 patients with positive anti-HCV antibodies and discernible HCV-RNA levels. Twentyfive patients were women and 23 were men. The control group included 100 healthy subjects. Forty-four were women and 56 were men. The polymorphisms were evaluated by polymerase chain reaction amplification (PCR), followed by the Restriction Fragment Length Polymorphism (RFLP) method. Results: The prevalence of the -308 TNF-á polymorphism was found to be 12% in patients with chronic hepatitis C and 20% in control subjects, (P=0.2616); whereas that of the -238 TNF-á polymorphism was found to be 2% and 12% in patients and control subjects, respectively (P=0.061). The TNF-á genotypes were found to be in Hardy-Weinberg equilibrium. Conclusions: No association was found between -308 and -238 TNF-á polymorphisms and chronic hepatitis C in the Mexican group studied. Our data suggest that additional studies increasing the sample size and a control group which has been exposed to an equal risk of infection are required to investigate whether these polymorphisms represent genetic susceptibility for chronic HCV infection. Key words: viral hepatitis, chronic hepatitis C, tumor necrosis factor alpha, genetic polymorphism, polymerase chain reaction.
[Show abstract][Hide abstract] ABSTRACT: The so-called tumor necrosis factor (TNF) block includes the TNFA, lymphotoxin alpha and beta (LTA and LTB) genes with single-nucleotide polymorphisms (SNP) and microsatellites with an allele frequency that exhibits interpopulation variability. To date, no reports have included both SNPs and microsatellites at the TNF block to study Mestizo or Amerindian populations from Mexico. In this study, samples of five Mexican Mestizo populations (Durango, Guadalajara, Monterrey, Puebla, and Tierra Blanca) and four native-Mexican populations (North Lacandonians, South Lacandonians, Tepehuanos, and Yaquis) were genotyped for two SNPs (LTA+252A>G and TNFA-308G>A) and four microsatellites (TNFa, d, e, and f), to analyze the genetic substructure of the Mexican population. Allele and haplotype frequencies, linkage disequilibrium (LD), and interpopulation genetic relationships were calculated. There was significant LD along almost all of the TNF block but the lowest D' values were observed for the TNFf-TNFd pair. Mestizos showed higher allele and haplotype diversity than did natives. The genetic differentiation level was reduced among Mestizos; however, a slightly, but significant genetic substructure was observed between northern and southern Mexican Mestizos. Among the Amerindian populations, the genetic differentiation level was significantly elevated, particularly in both North and South Lacandonians. Furthermore, among Southern Lacandonians, inhabitants of Lacanja town were the most differentiated from all the Mexicans analyzed. The data presented here will serve as a reference for further population and epidemiological studies including these TNF polymorphisms in the Mexican population.
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