Abstract
A functional single nucleotide polymorphism (SNP) of the PTPN22 gene encoding a protein tyrosine phosphatase has been associated with autoimmune disorders including myasthenia gravis (MG). As the PTPN22 R620W polymorphism has a wide variation of allele frequencies among different populations, this polymorphism was investigated in MG in Turkey. An emphasis is put on MG subgroups according to autoantibody (Abs) production and presence of thymoma. DNA samples from 416 patients with clinically diagnosed generalized MG (231 with Abs to acetylcholine receptor, AChR-MG), 53 with Abs to muscle-specific kinase (MuSK-MG), 55 patients with no detectable Abs (SN-MG), 77 patients with thymoma (TAMG) and 293 healthy controls (HC) were genotyped for the SNP (PTPN22 R620W, C1858T, rs2476601). The PTPN22 T allele was increased in AChR-MG patients (odds ratio [OR]: 2.5, 95%CI: 1.2–5.1). The association was stronger in late disease-onset AChR (LOMG, OR: 3.1, 95%CI: 1.2–8.2). MuSK-MG, SN-MG and TAMG groups did not carry the variant allele more frequently than the HC. In contrast to findings in other autoimmune diseases, the distribution of the PTPN22 polymorphism in this population provides a susceptibility marker for AChR-MG. The strongest association is detected in patients with LOMG.
Highlights
Acquired myasthenia gravis (MG) is a rare autoimmune disease which is clinically characterized by fatigability and weakness of striated muscles
The Protein tyrosine phosphatase non receptor 22 gene (PTPN22) R620W polymorphism is accepted as a general risk factor for autoimmune diseases with prominent production of auto-antibodies [15]
A relatively strong association of the polymorphic PTPN22 1858 T allele was demonstrated with acetylcholine receptor (AChR)-MG in this population from Turkey, where the minor allele frequency (MAF) of the polymorphic allele was as low as 2%
Summary
Acquired myasthenia gravis (MG) is a rare autoimmune disease which is clinically characterized by fatigability and weakness of striated muscles. The symptoms of MG are mediated mainly by pathogenic auto-antibodies (Abs) directed against the nicotinic acetylcholine receptor (AChR). These disease specific anti-AChR Abs are detected in the majority (80–85%) of the patients [1,2]. In a subgroup of MG patients without conventional anti-AChR Abs, Abs against the muscle-specific kinase (MuSK) are detected [3]. The agrin receptor low-density lipoprotein receptorrelated protein 4 (LRP4) has been identified as a novel target in a 2–50% of AChR and MuSK double seronegative patients [4,5,6]. The cut-off age between late-onset (LOMG) and early-onset MG (EOMG) has been shifted from 40 years [8] to 50 [9,10,11] and even to 60 years on the basis of clinical, histological and immunegenetic data [12,13,14]
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