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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

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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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Acknowledgements

The authors appreciate the kind help of the staff at the National Liver Institute, Cairo, Egypt for facilitating clinical samples and their data.

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Authors and Affiliations

  1. Genetic Engineering Division, Microbial Biotechnology Department, National Research Centre, El Behous st, Dokki, Cairo, Giza, 12311, Egypt

    Samar S. Youssef

  2. Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo, 11566, Egypt

    Nadia M. Hamdy

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  1. Samar S. Youssef
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  2. Nadia M. Hamdy
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Correspondence to Samar S. Youssef or Nadia M. Hamdy.

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Youssef, S.S., Hamdy, N.M. SOCS1 and pattern recognition receptors: TLR9 and RIG-I; novel haplotype associations in Egyptian fibrotic/cirrhotic patients with HCV genotype 4. Arch Virol 162, 3347–3354 (2017). https://doi.org/10.1007/s00705-017-3498-7

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