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Genetic variations in toll‐like receptors 7 and 8 modulate natural hepatitis C outcomes and liver disease progression
Author(s) -
Fakhir FatimaZohra,
Lkhider Mustapha,
Badre Wafaa,
Alaoui Rhimou,
Meurs Eliane F.,
Pineau Pascal,
Ezzikouri Sayeh,
Benjelloun Soumaya
Publication year - 2018
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13533
Subject(s) - allele , immunology , medicine , liver disease , innate immune system , hepatitis c virus , disease , immune system , snp , allele frequency , toll like receptor , genotype , virus , biology , single nucleotide polymorphism , gene , genetics
Background & Aims The natural outcomes of hepatitis C virus ( HCV ) as well as the progression of the liver disease are highly variable and depend primarily on an efficient immune response. As toll‐like receptors seven ( TLR 7) and eight ( TLR 8) are important effectors of the innate immunity, this study aims to evaluate the association between TLR 7 and TLR 8 polymorphisms and the HCV infection outcomes in Moroccan subjects. Methods In this case–control study, 643 subjects including 293 mild chronic hepatitis patients, 119 with advanced liver disease (Ad LD ), 93 with HCV spontaneous clearance and 138 healthy controls were genotyped using TaqMan SNP s assays. Results Patients carrying TLR 7 rs179008‐A allele were more likely to clear the virus spontaneously ( P = .0001 for women, and P < .001 for men). Besides, carriage of TLR 7 rs179009‐A allele was associated with a twofold increase in spontaneous viral clearance in female patients ( P = .0002), but not in men. In addition, we observed that TLR 7 rs179008‐T and rs179009‐G alleles increased the risk of disease progression in both sexes ( P < .05). TLR 8 rs3764880‐G allele was associated with spontaneous HCV clearance in both sexes ( P < .0001) albeit with an apparently stronger association in males ( OR = 6.02 for men vs 2.2 for women). In males, TLR 8 rs3764879‐C and TLR 8 rs3764880‐A alleles were significantly associated with Ad LD status ( P < .05). Conclusions Our results suggest that variations in TLR 7 and TLR 8 genes modulate the clearance and progression of HCV infection with different magnitudes between sexes. Our results refine, therefore, our understanding of the sex‐specific differences observed regarding the susceptibility to chronic hepatitis.