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SOCS1 and pattern recognition receptors: TLR9 and RIG-I; novel haplotype associations in Egyptian fibrotic/cirrhotic patients with HCV genotype 4

Authors
  • Youssef, Samar S.1
  • Hamdy, Nadia M.2
  • 1 National Research Centre, Genetic Engineering Division, Microbial Biotechnology Department, El Behous st, Dokki, Cairo, Giza, 12311, Egypt , Cairo, Giza (Egypt)
  • 2 Ain Shams University, Biochemistry Department, Faculty of Pharmacy, Abassia, Cairo, 11566, Egypt , Cairo (Egypt)
Type
Published Article
Journal
Archives of Virology
Publisher
Springer-Verlag
Publication Date
Jul 31, 2017
Volume
162
Issue
11
Pages
3347–3354
Identifiers
DOI: 10.1007/s00705-017-3498-7
Source
Springer Nature
License
Yellow

Abstract

In this paper we explore the role of suppressor of cytokine signaling 1 (SOCS1) (rs243327), the regulator of toll-like receptor-9 (TLR9) (rs352140), retinoic acid inducible gene-I (RIG-I) (rs669260), and cluster of differentiation 152 (CD152) (rs231776) in fibrotic/cirrhotic patients. Single nucleotide polymorphisms (SNPs) within these genes as well as haplotype analyses were performed on a cohort of 120 Egyptian fibrotic patients. Fibrosis had progressed from HCV genotype 4 infections. Using RT-PCR, SNPs were evaluated in the DNA collected from each patient using TaqMan® genotyping assays. A regression model was used to evaluate allelic and haplotypic associations with a fibrosis/cirrhotic scale. The necroinflammatory A score was adjusted for non-genetic covariates. The genotype distributions for SOCS1 (rs243327) and TLR-9 (rs352140) differed significantly between the F1-F3 and F3-F4 groups. On the other hand, the genotype distributions for RIG-I (rs669260) and CD152 (rs231776) genes did not significantly differ. The allele frequency was calculated using Hardy-Weinberg Equilibrium (HWE) for the SOCS1 (rs243327), RIG-I (rs669260), and CD152 (rs231776) genes. These calculated frequency values indicated the need to compare them to another population for that locus. However, TLR9 (rs352140) did not show similar results. The A allele in SOCS1, TLR9, and RIG-I SNPs was an adverse prognostic factor for liver fibrosis and liver activity. Haplotype analysis revealed a significant association between SOCS1 and TLR9 in fibrotic/cirrhotic patients. This indicated the presence of the A allele in either gene, which is considered a risk factor for the progression of liver disease to cirrhosis. SOCS1 rs243327, TLR9 rs352140, and RIG-I rs669260 polymorphisms might affect liver pathophysiology and the cirrhotic outcome following genotype 4 HCV infection. Therefore, performing this specific SNP testing may be of value for the stratification of the population at risk.

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