Genetic variations of NOD2 and MD2 genes in hepatitis B virus infection |
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| Authors: | Mashael R Al-Anazi Nyla Nazir Ayman A Abdo Faisal M Sanai Saad Alkahtani Saud Alarifi Abdullah A Alkahtane Hamad Al-Yahya Daoud Ali Mohammed S Alessia Mohammed N Al-Ahdal Ahmed A Al-Qahtani |
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| Institution: | 1. Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia;2. Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia;3. Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia;4. Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia;5. Department of Biology, Science College, AI-Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia;6. Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia;7. Department of Microbiology and Immunology, Alfaisal University School of Medicine, Riyadh, Saudi Arabia |
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| Abstract: | Objectives: Nucleotide oligomerization domain 2 (NOD2) and myeloid differentiation protein 2 (MD-2) have crucial roles in the innate immune system. NOD2 is a member of the NOD-like receptor (NLR) family of pattern recognition receptors (PRRs), while MD-2 is a co-receptor for Toll-like receptor 4 (TLR4), which comprises another group of PRRs. Genetic variations in the NOD2 and MD-2 genes may be susceptibility factors to viral pathogens including hepatitis B virus (HBV). We investigated whether polymorphisms at NOD2 (rs2066845 and rs2066844) or at MD-2 (rs6472812 and rs11466004) were associated with susceptibility to HBV infection and advancement to related liver complications in a Saudi Arabian population. Methods: A total of 786 HBV-infected patients and 600 healthy uninfected controls were analyzed in the present study. HBV-infected patients were categorized into three groups based on the clinical stage of the infection: inactive HBV carriers, active HBV carriers, and patients with liver cirrhosis + hepatocellular carcinoma (HCC). Results: All four SNPs were significantly associated with susceptibility to HBV infection although none of the SNPs tested in NOD2 and MD-2 were significantly associated with persistence of HBV infection. We found that HBV-infected patients that were homozygous CC for rs2066845 in the NOD2 gene were at a significantly increased risk of progression to HBV-related liver complications (Odds Ratio = 7.443 and P = 0.044). Furthermore, haplotype analysis found that the rs2066844-rs2066845 C-G and T-G haplotypes at the NOD2 gene and four rs6472812-rs11466004 haplotypes (G-C, G-T, A-C, and A-T) at the MD-2 gene were significantly associated with HBV infection in the affected cohort compared to those found in our control group. Conclusion: We found that the single nucleotide polymorphisms rs2066844 and rs2066845 at NOD2 and rs6472812 and rs11466004 at MD-2 were associated with susceptibility to HBV infection in a Saudi population. |
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| Keywords: | NOD2 MD-2 SNP Hepatitis B virus Saudi |
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