High prevalence of protein tyrosine phosphatase non-receptor N22 gene functional variant R620W in systemic lupus erythematosus patients from Kuwait: implications for disease susceptibility

Abstract

Background Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease which involves the loss of self-tolerance with hyperactivation of autoreactive T- and B-cells. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) encodes for lymphoid specific phosphatase (LYP) which is a key negative regulator of T lymphocyte activation. The aim of this study was to investigate the association between PTPN22 gene functional variant R620W and systemic lupus erythematosus (SLE) by comparing its prevalence in Kuwaiti SLE patients and controls. Methods The study included 134 SLE patients and 214 controls from Kuwait. The genotypes of PTPN22 gene functional variant R620W were determined by PCR-RFLP and confirmed by DNA sequence analysis in both SLE patients and the controls. Results A relatively high prevalence of the variant 620 W (T-allele) of the PTPN22 gene was detected in the SLE patients from Kuwait. 35.7% of the SLE patients had at least one variant allele (T-allele) compared to 15.9% in the controls. A statistically significant difference was detected in the frequency of variant genotypes, TT and CT between SLE patients and the controls ( p < 0.0001). No association was detected between the PTPN22 gene variant and the Raynaud’s phenomenon, renal involvement and severity of the SLE. Conclusions The frequency of PTPN22 gene functional variant R620W reported in this study is amongst the highest compared to other world populations. A high prevalence of this variant in SLE patients in comparison to the healthy controls suggests its significant contribution in conferring susceptibility to SLE together with other factors.

Protein tyrosine phosphatase non‐receptor type 22 (PTPN22) gene polymorphisms in liver transplant donors and impact on acute cellular liver transplant rejection

“…Such differences have been described in some studies, at least for the SNPs rs2476601 and rs1310182, thus, our sample size appears appropriate to identify existing associations. [34][35][36] In summary, our data reveal no evidence of an association between the SNPs rs1217388, rs1310182, rs2476601, and rs2488457 of the PTPN22 gene in liver transplant donors and acute cellular liver transplant rejection. We suggest that these SNPs in liver transplant donors have no impact on the susceptibility to develop acute cellular liver transplant rejection.…”

“…However, our sample size is sufficient to capture an allele difference (no‐BPACR vs BPACR) of 16% for rs1217388, 17% for rs1310182, 12% for rs2476601, and 16% for rs2488457 with a power of >80%. Such differences have been described in some studies, at least for the SNPs rs2476601 and rs1310182, thus, our sample size appears appropriate to identify existing associations …”

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

“…38 Our results were consistent with that reported in many different populations as in USA, 20 Sweden, 39 Spain 40 and Kuwait. 41 It was also found that sporadic childhood-onset SLE Mexican population was associated with PTPN22 1858 T allele. 42 Ostanek, et al; 2014 43 observed that the presence of at least one T allele carries higher susceptibility to SLE among Polish population and that was similar to our observation regard heterozygous TC genotype.…”

Lupus nephritis: A focus on the United Arab Emirates and the potential role of genetics

“…Genetic studies of SLE among Arab patients in the GCC region are generally scarce in the literature, and extremely rare regarding LN. Some of SLE susceptibility genes have been recently reported and/or investigated in SLE patients in the GCC region, such as HLA alleles, 29,30 C1Q, 31,32 ISG15, 33 APOE, 34 PTEN, 35 and PNP 36 genes in Saudi patients; and IRF5, 37 PTPN22, 38 ACE, 39 eNOS, 40,41 and CTLA4 42,43 genes in Kuwaiti patients. Of note, Al-Mayouf et al 44 identified a rare autosomal recessive monogenic form of SLE in Arab patients in Saudi Arabia, caused by a null mutation in the DNASE1L3 gene, and correlated with a high frequency of LN.…”