Association between IL-37 gene polymorphisms and risk of HBV-related liver disease in a Saudi Arabian population
Al-Anazi MR1, Matou-Nasri S2, Al-Qahtani AA3, Alghamdi J2, Abdo AA4,5, Sanai FM6,5, Al-Hamoudi WK4,5, Alswat KA4,5, Al-Ashgar HI7, Khan MQ7, Albenmousa A8, Shamsi MB9, Alanazi SK1, Dela Cruz D1, Bohol MFF1, Al-Ahdal MN1,10, Al-Qahtani AA11,12.
1 Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
2 Medical Genomics Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
3 Department of Family Medicine, Prince Mohammed Bin Abdul Aziz Hospital, Riyadh, Saudi Arabia.
4 Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
5 Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia.
6 Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia.
7 Gastroenterology Unit, Department of Medicine, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
8 Department of Gastroenterology, Prince Sultan Medical Military City, Riyadh, Saudi Arabia.
9 Centre for Genetics and Inherited Diseases, College of Medicine, Taibah University, Madinah, Saudi Arabia.
10 Department of Microbiology and Immunology, Alfaisal University School of Medicine, Riyadh, Saudi Arabia.
11 Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
12 Department of Microbiology and Immunology, Alfaisal University School of Medicine, Riyadh, Saudi Arabia.
Year of Publication:
Interleukin-37 (IL-37) has recently been recognized as a strong anti-inflammatory cytokine having anti-tumor activity against hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients. HCC is a typical inflammation-related cancer, and genetic variations within the IL-37 gene may be associated with the risk of HBV infection. Identification of the allelic patterns that genetically have a high disease risk is essential for the development of preventive diagnostics for HBV-mediated liver disease pathogenesis. In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within the IL-37 gene and disease sequelae associated with HBV infection. We genotyped ten IL-37 SNPs in 1274 patients infected with HBV and 599 healthy controls from a Saudi Arabian population. Among the selected SNPs, two SNPs (rs2723175 and rs2708973) were strongly associated with HBV infection, and six SNPs (rs2723176, rs2723175, rs2723186, rs364030, rs28947200, rs4392270) were associated with HBV clearance, comparing healthy controls and HBV infected-patients respectively. A suggestive association of rs4849133 was identified with active HBV surface antigen (HBsAg) carrier and HBV-related liver disease progression. In conclusion, our findings suggest that variations at the IL-37 gene may be useful as genetic predictive risk factors for HBV infection and HBV-mediated liver disease progression in the Saudi Arabian population.