Geographical distribution and disease associations of the CD45 exon 6 138G variant

Abstract

CD45 is crucial for normal lymphocyte signalling, and altered CD45 expression has major effects on immune function. Both mice and humans lacking CD45 expression are severely immunodeficient, and single-nucleotide polymorphisms in the CD45 gene that cause altered splicing have been associated with autoimmune and infectious diseases. Recently, we identified an exon 6 A138G polymorphism resulting in an increased proportion of activated CD45RO T cells and altered immune function. Here we report a significantly reduced frequency of the 138G allele in hepatitis C Japanese patients and a possibly reduced frequency in type I diabetes. The allele is widely distributed in the Far East and India, indicating that it may have a significant effect on disease burden in a large part of the human population.

PTPRC (CD45) variation and disease association studied using single nucleotide polymorphism tagging

“…Employing a set of tagSNP markers covering the whole length of the gene, we have investigated whether other variations in the gene were associated with diseases such as type 1 diabetes, Graves' disease in the JPT population, tuberculin response and worm burden in the Chinese population and HCV in CEU population. No stronger or novel signals of association than previously reported for Graves' disease and diabetes (3,4) were discovered, apart from one intronic SNP (rs6683595) that showed some LD with the exonic SNP A138G. We also showed that most of the 138G allele is present in one common haplotype.…”

“… a The table shows the SNP identification number, location in the PTPRC gene, amino acid residue affected and minor allele frequencies (MAF as percentage) in the HapMap Japanese (JPT), Han Chinese (CHB) and US Caucasian (CEU) samples (11) and our own Japanese controls (4), whole Chinese sample cohort (21) and UK blood donors (22). All polymorphisms were genotyped by Sequenom hME Mass‐Array primer extension assay (http://www.sequenom.de/) (24) under standard conditions.…”

Genetic predisposition and environmental danger signals initiate chronic autoimmune hepatitis driven by CD4+T cells

“…In detail, a predisposition of extended HLA‐DRB1 alleles like DRB1*0301, DRB1*0401, DRB1*0404, and DRB1*0405 can be found in patients with AIH as well as patients with type 1 diabetes . In addition, non‐HLA susceptibility genes like CTLA‐4 (IDDM12), CD45, TNF‐α, or vitamin D receptor (IDDM34) are associated with the development of type I diabetes and were also associated with the development of AIH . Taken together, the use of the NOD strain for successful induction of emAIH underlines the importance of these genetic associations for the induction of AIH.…”

Alternative splicing in multiple sclerosis and other autoimmune diseases

“…Considering that the longer isoforms are associated with more efficient TCR signaling, failure to attenuate prolonged TCR activation could contribute to the inflammatory response resulting in axon demyelination in MS. In contrast, the nonsynonymous SNP 138G→A in exon 6 results in increased production of the shorter isoform CD45RO, 55,56 with the "G" allele having a significant protective effect in Graves' disease, another autoimmune disorder. 55 Other studies, however, have argued against a significant association between CD45 and MS. [57][58][59][60][61][62] Alternative splicing of CD45 is one of the best-characterized splicing events in the immune system, both at the level of cis-acting regulatory elements, 63 and trans-acting protein factors.…”