Tumor necrosis factor receptor II and PTPN22 genes polymorphisms and the risk of systemic lupus erythematosus in Egyptian children

Abstract

Background Many genes have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF) is a potent cytokine stimulator acting through 2 cell surface receptors (TNFR I and II). TNFRII gene which controls expression of these receptors has been linked to SLE susceptibility through promoting apoptosis. Also; Protein tyrosine phosphatase non receptor 22 (PTPN22) gene enhances intrinsic phosphatase activity of T lymphocytes leading to their dysregulation and stimulates autoimmune process of lupus and its rs2476601 has been linked to susceptibility to thyroiditis in SLE patients in few studies. Objectives (i) to investigate the correlation between 2 SNPs of TNFR II and PTPN22 genes and SLE susceptibility in a cohort of Egyptian children compared to controls (ii) and to investigate their possible association with different clinical presentations of the disease in children. Subjects and methods Typing of TNFR II rs1061622 and PTPN22 rs2476601 SNPs were done using polymerase chain reaction-restriction fragment length polymorphism for 74 children with SLE and 100 matched healthy controls. Results Children with SLE had more frequent G allele and GG genotype of TNFR II rs1061622 ( p < 0.001) and more T allele and TT genotype of PTPN22 rs2476601 ( p = 0.012 and <0.001, respectively) compared to controls. Only 6 patients (8%) had thyroiditis (hypothyroidism) with T allele and TT genotype of PTPN22 1858 T more prevalent in those patients versus those without thyroiditis ( p ≤ 0.001). Apart from, thyroiditis, no significant association was found between genotypes and alleles frequencies of the 2 studied SNPs and other clinical manifestations of the disease. Conclusion The G allele and GG genotype of TNFR II rs1061622 and T allele and TT genotype of PTPN22 rs2476601 genes polymorphism can be considered as risk factors for the development of SLE. The presence of the T allele of PTPN22 rs2476601 may increase the risk of concomitant thyroiditis in Egyptian children with SLE but further studies are required to confirm this finding as thyroiditis was reported only in few cases in this study.

Association Between Foxp3 (Rs3761548) Promoter Polymorphism With Vitiligo Patients, Their Clinical Data and Response to Phototherapy: A Study From Egypt

“…On the other hand, the loss may be due to inbreeding, deletion polymorphism, copy number variation, or purifying selection. The reduction of heterozygosity may be due to the prevalence of consanguineous marriage in the Egyptian community 57 , and this may explain the deviation from HWE in this study.…”

Interactions between TNFAIP3, PTPN22, and TRAF1-C5 gene polymorphisms in patients with primary Sjögren's syndrome

“…[12][13][14][15][16][17][18][19][20] From the point of view of genetic susceptibility, we have recently reported associations of PTPN22 SNPs with RA, SLE, and Graves' disease in patients from Mexico. 14,15 PTPN22 is a risk factor for RA, SLE, and pSS, primarily in Caucasian and Latin American populations; 14,15,[23][24][25][26] meanwhile, TNFAIP3 is a risk factor for RA, SLE, and pSS, mainly in Asian and Caucasian populations. 4,7,18,27,28 Finally, TRAF1-C5 has been reported to be a risk factor for RA and SLE in Africans and Caucasians.…”

Impact of TNFRSF1B (rs3397, rs1061624 and rs1061622) and IL6 (rs1800796, rs1800797 and rs1554606) Gene Polymorphisms on Inflammatory Response in Patients with End-Stage Kidney Disease Undergoing Dialysis

“…The TNFRSF1B rs1061622 SNP has been associated with some inflammatory disorders [ 10 , 14 , 15 ]. In the case of psoriasis, an inflammatory dermatologic disease, the TNFRSF1B rs1061622 SNP was reported to be associated with the risk of developing this disease and with the response to psoriasis treatment with anti-TNF or anti-IL12/IL23 agents [ 36 ]; in patients with COVID-19, the GG carriers presented significantly lower levels of sTNFR1 and a trend towards lower values of sTNFR2 compared to those with the TT and TG genotypes [ 10 ]; subjects with rheumatoid arthritis did not present differences in sTNFR2 concentrations between TNFRSF1B rs1061622 SNP genotypes [ 13 ].…”

“…The rs1061624 TNFRSF1B polymorphism was reported to be implicated in the development of arterial hypertension in men [ 11 ] and associated with long-term response to infliximab in patients with Crohn’s disease [ 12 ]. Another single-nucleotide polymorphism (SNP), TNFRSF1B rs1061622 (+676 T>G), which results in an amino acid change at position 196 (methionine/arginine), was associated with higher levels of sTNFR2 in inflammatory conditions, such as rheumatoid arthritis [ 13 ], systemic lupus erythematosus [ 14 ], and preeclampsia [ 15 ].…”