Marwa Chaouali1, Veronica Fernandes2, Ezzedine Ghazouani3, Luisa Pereira4, Radhia Kochkar3. 1. Department of Immunology, Military Hospital of Tunis, Montfleury 1008, Tunis, Tunisia; Laboratory of Mycology Pathologies and Biomarkers, El Manar University, Tunis 1092, Tunisia. Electronic address: marouachaouali@gmail.com. 2. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto 4200-135, Portugal. 3. Department of Immunology, Military Hospital of Tunis, Montfleury 1008, Tunis, Tunisia. 4. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal; Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto 4200-135, Portugal; Faculdade de Medicina da Universidade do Porto, Portugal.
Abstract
The physiopathology of autoimmune hepatitis (AIH) is complex and still not fully elucidated. The genes localized outside the histocompatibility complex involved in regulation and signal transduction of the immune system SH2B3, TGFβ1, STAT4 and PTPN22 could be associated to the susceptibility and hepatocyte lysis mechanism of this lethal autoimmune disorder. PATIENTS AND METHODS: We investigated four polymorphic sites in SH2B3 (rs3184504), TGFβ1 (rs1800471), STAT4 (rs7574865) and PTPN22 (rs2476601) in 45 AIH patients and 150 healthy controls from Tunisia using real-time PCR. RESULTS: Significant associations were found for SH2B3 T allele (OR = 1.861; p = 0.015, pc = 0.366) and PTPN22 A allele (OR = 7.070; p = 0.026; pc = 1.00) and AIH with opposite homozygous being protective against the disease (CC genotype with OR = 0.420, p = 0.025; GG genotype with OR = 0.136, p = 0.025, respectively). No statistically significant associations were found for the TGFβ1 and STAT4 polymorphisms with AIH susceptibility. CONCLUSION: Our work enlarges information on non-HLA genes that are associated with AIH by focusing in a region of the world that was poorly molecularly characterized for this disease.
The physiopathology of autoimmune hepatitis (AIH) is complex and still not fully elucidated. The genes localized outside the histocompatibility complex involved in regulation and signal transduction of the immune system SH2B3, TGFβ1, STAT4 and PTPN22 could be associated to the susceptibility and hepatocyte lysis mechanism of this lethal autoimmune disorder. PATIENTS AND METHODS: We investigated four polymorphic sites in SH2B3 (rs3184504), TGFβ1 (rs1800471), STAT4 (rs7574865) and PTPN22 (rs2476601) in 45 AIH patients and 150 healthy controls from Tunisia using real-time PCR. RESULTS: Significant associations were found for SH2B3 T allele (OR = 1.861; p = 0.015, pc = 0.366) and PTPN22 A allele (OR = 7.070; p = 0.026; pc = 1.00) and AIH with opposite homozygous being protective against the disease (CC genotype with OR = 0.420, p = 0.025; GG genotype with OR = 0.136, p = 0.025, respectively). No statistically significant associations were found for the TGFβ1 and STAT4 polymorphisms with AIH susceptibility. CONCLUSION: Our work enlarges information on non-HLA genes that are associated with AIH by focusing in a region of the world that was poorly molecularly characterized for this disease.
Authors: Mohamed M Zedan; Zeinab Rizk Attia; Rania A Abd El Azeem; Thuraya M Mutawi; Amora S El Shehawy; Ashraf Bakr Journal: J Inflamm Res Date: 2021-07-15