M El-Bendary1, M Neamatallah2, H Elalfy1, T Besheer1, A Elkholi3, M El-Diasty1, M Elsareef4, M Zahran5, B El-Aarag4, A Gomaa6, D Elhammady1, M El-Setouhy7, A Hegazy8, G Esmat9. 1. a Tropical Medicine and Hepatology Department, Faculty Of Medicine , Mansoura University , Mansoura , Egypt. 2. b Medical Biochemistry Department, Faculty of Medicine , Mansoura University , Mansoura , Egypt. 3. c Gastroenterology Department , Health Insurance Hospital , Mansoura , Egypt. 4. d Biochemistry Division, Chemistry Department, Faculty of Science , Menoufia University , Shebin El-Koom , Egypt. 5. e Chemistry Department, Faculty of Science , Menoufia University , Shebin El-Koom , Egypt. 6. f Zoology Department, Faculty of Science , Alazhar University , Cairo , Egypt. 7. g Department of Community, Environmental, and Occupational Medicine, Faculty of Medicine , Ain-Shams University, Cairo, Egypt; Substance Abuse Research Center (SARC), Jazan University , Jazan , Kingdom of Saudi Arabia. 8. h Internal Medicine Department, Faculty of Medicine , Alazhar University , Cairo , Egypt. 9. i Endemic Medicine and Endemic Hepatogastroenterology Department, Faculty of Medicine , Cairo University , Cairo , Egypt.
Abstract
BACKGROUND: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection. MATERIALS & METHODS: A total of 3368 subjects from 850 families were recruited and divided into three main groups categorized as chronic HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using allelic discrimination real-time PCR. RESULTS: Carriage of the C allele in three SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7 (rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only were significantly higher in SVC group than CHC group (P < 0.001), while carriage of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both males and females were significantly higher in CHC infection more than SVC group (P < 0.001). CONCLUSION: The C allele is protective of HCV in TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while risk of infection is linked to the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both sexes.
BACKGROUND: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection. MATERIALS & METHODS: A total of 3368 subjects from 850 families were recruited and divided into three main groups categorized as chronic HCV CHC spontaneous viral clearance (SVC), and controls. All individuals were genotyped for three SNPs for TLR3, two SNPs for TLR7, and two SNPs for TLR8 using allelic discrimination real-time PCR. RESULTS: Carriage of the C allele in three SNPs of TLR3 (rs3775290, rs3775291, and rs5743312), the C allele in TLR7 (rs3853839) in females only, and the C allele in TLR8 (rs3764879) in males only were significantly higher in SVC group than CHC group (P < 0.001), while carriage of the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both males and females were significantly higher in CHC infection more than SVC group (P < 0.001). CONCLUSION: The C allele is protective of HCV in TLR3, TLR7 (rs3853839) in females only, and TLR8 (rs3764879) in males only, while risk of infection is linked to the T allele in TLR7 (rs179008) in females only and the A allele in TLR8 (rs3764880) in both sexes.