Association study of PTPN22 gene polymorphism with Rheumatoid Arthritis in Vindhyan Population

Abstract

Rheumatoid arthritis is a complex disease in which combinations of multiple genetic and non-genetic factors determine susceptibility. It is symmetric, chronic polyarticular arthritis that affects 0.5-1% of the population. PTPN22 encodes for an 807 amino acid residue protein called LYP (lymphoid tyrosine phosphatase), which has been shown to negatively regulate T-cell signaling. A single-nucleotide polymorphism in the PTPN22 gene at nucleotide position 1858 C4T (codon 620), resulting in an arginine-to-tryptophan (CGG to TGG) transition, has been shown to be a gain-of-function mutation, with a more potent negative regulation of T-cell signaling through reduced Lck (leukocyte-specific protein tyrosine kinase)-mediated phosphorylation of the TCRx chain, reduced tyrosine phosphorylation of LAT (linker for activation of T cells), and reduced activation of Erk2. The mutant, LYP-Trp620, has been associated with several autoimmune diseases. PCR is a rapid, inexpensive and simple mean of producing relatively large copy number of DNA molecules from the small amounts of source DNA material, even when the source DNA is of relatively poor quality. The oligonucleotides sequences (primers) were designed to create a recognition site for the restriction enzyme XcmI in the T allele. Overall allele ‘C’ was found to be in significantly low frequency in disease group as compared to HC group whereas allele ‘T’was present in significantly high frequency in the disease group (χ2 = 11.88; d.f. =1; P=0.0006)..Carriage rate of allele ‘C’ was equivalent to HC group and RA group. Whereas carriage rate of allele ‘T’ was high in disease group (χ2 =s, d.f. = 1; P=0.).