Fatemeh Tahghighi1, Vahid Ziaee2, Mohammad Hassan Moradinejad3, Arezou Rezaei4, Sara Harsini4, Samaneh Soltani5, Maryam Sadr5, Maryam Mahmoudi6, Yahya Aghighi7, Nima Rezaei8. 1. Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. 2. Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran; Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 4. Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 5. Molecular Immunology Research Center, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. 6. School of Nutrition and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. 7. Department of Pediatrics, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. 8. Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Molecular Immunology Research Center, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: rezaei_nima@tums.ac.ir.
Abstract
BACKGROUND: Juvenile systemic lupus erythematosus (JSLE) is a multi-system autoimmune disorder of unknown origin. Given the importance of the contribution of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), towards the pathogenesis of JSLE, this study was performed to assess TNFA gene polymorphisms in a case-control study. METHODS: Fifty nine patients with JSLE were enrolled in this study as case group and compared with healthy control subjects. The frequency of alleles, genotypes, and haplotypes of TNFA single-nucleotide polymorphisms (SNPs) at positions -308 and -238 were evaluated, using polymerase chain reaction with sequence-specific primers method. RESULTS: The G allele at position -238 in TNFA promoter region was significantly more frequent in patients with JSLE than in the healthy controls (P value<0.001), while the frequency of A allele at the same position was significantly lower than controls. Furthermore, a significant positive association for G/G genotype at the same position was detected in patients' group compared with control subjects (P value<0.001). The GA haplotype of TNFA (positions -308, -238) was significantly less frequent in case group than in controls (P value<0.001), while GG was the most frequent haplotype for TNFA in the patient group, compared to controls (P value<0.01). CONCLUSIONS: Pro-inflammatory cytokine gene polymorphisms may influence susceptibility to JSLE. Particular TNFA gene variants are associated with JSLE and could be used as a genetic marker for susceptibility to JSLE.
BACKGROUND:Juvenile systemic lupus erythematosus (JSLE) is a multi-system autoimmune disorder of unknown origin. Given the importance of the contribution of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), towards the pathogenesis of JSLE, this study was performed to assess TNFA gene polymorphisms in a case-control study. METHODS: Fifty nine patients with JSLE were enrolled in this study as case group and compared with healthy control subjects. The frequency of alleles, genotypes, and haplotypes of TNFA single-nucleotide polymorphisms (SNPs) at positions -308 and -238 were evaluated, using polymerase chain reaction with sequence-specific primers method. RESULTS: The G allele at position -238 in TNFA promoter region was significantly more frequent in patients with JSLE than in the healthy controls (P value<0.001), while the frequency of A allele at the same position was significantly lower than controls. Furthermore, a significant positive association for G/G genotype at the same position was detected in patients' group compared with control subjects (P value<0.001). The GA haplotype of TNFA (positions -308, -238) was significantly less frequent in case group than in controls (P value<0.001), while GG was the most frequent haplotype for TNFA in the patient group, compared to controls (P value<0.01). CONCLUSIONS: Pro-inflammatory cytokine gene polymorphisms may influence susceptibility to JSLE. Particular TNFA gene variants are associated with JSLE and could be used as a genetic marker for susceptibility to JSLE.
Authors: Mohammad Jafar Mahmoudi; Sara Harsini; Elham Farhadi; Mona Hedayat; Mohammad Taghvaei; Maryam Mahmoudi; Maryam Sadr; Nilufar Esfahanian; Ebrahim Nematipour; Keramat Nourijelyani; Ali Akbar Amirzargar; Nima Rezaei Journal: Avicenna J Med Biotechnol Date: 2018 Jul-Sep