Genetic variations of NOD2 and MD2 genes in hepatitis B virus infection.

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 and genes may be susceptibility factors to viral pathogens including hepatitis B virus (HBV). We investigated whether polymorphisms at (rs2066845 and rs2066844) or at (rs6472812 and rs11466004) were associated with susceptibility to HBV infection and advancement to related liver complications in a Saudi Arabian population. 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). All four SNPs were significantly associated with susceptibility to HBV infection although none of the SNPs tested in and were significantly associated with persistence of HBV infection. We found that HBV-infected patients that were homozygous CC for rs2066845 in the gene were at a significantly increased risk of progression to HBV-related liver complications (Odds Ratio = 7.443 and  = 0.044). Furthermore, haplotype analysis found that the rs2066844-rs2066845 C-G and T-G haplotypes at the gene and four rs6472812-rs11466004 haplotypes (G-C, G-T, A-C, and A-T) at the gene were significantly associated with HBV infection in the affected cohort compared to those found in our control group. We found that the single nucleotide polymorphisms rs2066844 and rs2066845 at and rs6472812 and rs11466004 at were associated with susceptibility to HBV infection in a Saudi population.