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IL-17 Genetic Variations Increase the Risk of Cirrhotic/Hepatocellular Carcinoma in Patients with Hepatitis B Virus Infection.
Authors:Abolfazl  GheshlaghiMohammad Reza  HaghshenasAli Reza  SafarpourSeyed Younes  HossiniSeyed Ali  MalekhosseiniMohammad Reza  FattahiJamal  Sarvari
Institution:1Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran2Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran3Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran4Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract:Background: Genetic variation in immune regulatory genes might influence the HBV infection outcome. Objective: This study aimed to determinethe association of IL-17A rs2275913 (G197A), IL-17F rs763780 (A7488G), and IL-23R rs10889677 (C2370A) gene polymorphisms, as well as the emerged haplotypes in the individual infected by HBV and to investigate their association with the infection outcome. Materials and Methods: 300 chronic HBV infections with Cirrhotic/Hepatocellular carcinoma (C/HCC), chronic active (CA), and asymptomatic carrier (AC) and 38 individuals whose infection was spontaneously cleared (SC) were enrolled. Genomic DNA was extracted, and IL-17A/F and IL-23R genotyping were performed by using the PCR-RFLP method. Results: Out of 338 subjects, 238 and 100 were respectively male and /female with a mean age of 47.61±13.41. The frequency of GA genotype (p=0.01) and A alleles (p=0.001) of IL-17A rs2275913 (G197A), as well as the frequency of AA genotype (p=0.014) and A alleles (p=0.018) of IL-17F rs763780 (A7488G) gene locus, was found to be significantly higher in the C/HCC than CA and AC groups. Furthermore, the frequency of GA and AG haplotype in CA individuals was higher than those with C/HCC and AC (p=0.003). Also, the GG haplotype was higher in AC individuals than those with C/HCC (P=0.022), and the AA haplotype was higher in C/HCC individuals than the CA patients (P=0.001). Conclusion: Our findings suggest that A allele and GA genotype at IL-17A rs2275913 (G197A), as well as A allele and AA genotype at IL-17F rs763780 (A7488G) locus, might be associated with increased risk of C/HCC among patients with hepatitis B virus infection.
Keywords:Cirrhotic/Hepatocellular carcinoma  HBV  IL-17 genetic variation
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