TNF-α -308 G>A and IL10 -1082A>G polymorphisms as potential risk factors for lymphoproliferative disorders in autoimmune rheumatic diseases
Autor: | Aida Nazir, Ibtessam M. Abdelhamid, Amira I. Fayad, Manal Y. Tayel, Nadia E. Zaki, Nehad S. Elsharkawy, Myriam Helmy |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty lcsh:QH426-470 Lymphoproliferative diseases (LPD) medicine.medical_treatment Lymphoproliferative disorders Single-nucleotide polymorphism Gastroenterology Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Internal medicine Genotype medicine Risk factor Allele PCR-sequence-specific primer (PCR-SSP) Autoimmune rheumatic disease (ARD) Genetics (clinical) 030203 arthritis & rheumatology lcsh:R5-920 business.industry Haplotype Single nucleotide polymorphisms (SNPs) medicine.disease lcsh:Genetics 030104 developmental biology Cytokine Cytokines business lcsh:Medicine (General) |
Zdroj: | Egyptian Journal of Medical Human Genetics, Vol 21, Iss 1, Pp 1-13 (2020) |
ISSN: | 2090-2441 |
Popis: | Background Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α -308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs -1082 A>G, -819T>C, and -592A>C; IL-6 -174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCR-sequence-specific primer (PCR-SSP). Results ARD+LPD patients had significantly higher frequency of TNF-α -308A allele and AA+AG genotype (high TNF-α producers) and IL-10 -1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). Conclusion The significantly increased frequency of the high-TNF-α- and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development. |
Databáze: | OpenAIRE |
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