TNF-α -308 G>A and IL10 -1082A>G polymorphisms as potential risk factors for lymphoproliferative disorders in autoimmune rheumatic diseases

BackgroundChronic 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...

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Published in:	Egyptian Journal of Medical Human Genetics Vol. 21; no. 1; pp. 2 - 13
Main Authors:	Tayel, Manal Y, Nazir, Aida, Abdelhamid, Ibtessam M, Helmy, Myriam A. S, Zaki, Nadia E, Elsharkawy, Nehad S, Fayad, Amira I
Format:	Journal Article
Language:	English
Published:	Cairo Springer Nature B.V 10-01-2020 SpringerOpen
Subjects:	Alleles Autoimmune rheumatic disease (ARD) Cytokines Erythrocyte sedimentation rate Genotyping Haplotypes Immunoproliferative diseases Inflammation Interleukin 1 Interleukin 10 Interleukin 6 Joint diseases Lymphatic diseases Lymphocytes Lymphoproliferative diseases (LPD) Malignancy PCR-sequence-specific primer (PCR-SSP) Rheumatic diseases Risk factors Single nucleotide polymorphisms (SNPs) Single-nucleotide polymorphism Systemic lupus erythematosus Transforming growth factor-b1 Tumor necrosis factor-α γ-Interferon United States > US
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Summary:	BackgroundChronic 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).ResultsARD+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).ConclusionThe 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.
ISSN:	1110-8630 2090-2441
DOI:	10.1186/s43042-019-0043-0