Association of PTPN22 haplotypes with Graves' disease.
BACKGROUND
A recent study reported associations of a series of single nucleotide polymorphisms (SNPs) within PTPN22, including rs2476601, with rheumatoid arthritis.


OBJECTIVE
Having previously reported significant association of the T allele of rs2476601 in a Graves' disease (GD) cohort, we sought to determine whether novel rheumatoid arthritis-associated SNPs were also contributing to susceptibility to GD.


METHODS
Case control and family-based studies of five PTPN22 tag SNPs were performed.


METHODS
An United Kingdom academic department of medicine was the setting for the study.


METHODS
A total of 768 GD patients, 768 control subjects, and 313 families with autoimmune thyroid disease participated.


METHODS
Tests for association with disease were the main outcome measure.


RESULTS
No association with disease of any of the individual SNPs and no correlation between genotype and clinical phenotype were seen. However, haplotype analysis of the SNP markers with addition of rs2476601 did reveal a strong association of a haplotype containing the T allele, in both the case control (chi2 = 29.13; P = 6.77 x 10(-8)) and family data sets (chi2 = 5.24; P = 0.02). Furthermore, a novel protective effect of a haplotype containing all six SNPs was observed (chi2 = 17.02; P = 3.7 x 10(-5)).


CONCLUSIONS
These data suggest that the association of SNPs within the PTPN22 region differs between autoimmune diseases, occurring individually and/or as part of a haplotype, indicating that the mechanisms by which PTPN22 confers susceptibility to GD may, in part, be disease specific.
Heward
Joanne M
JM
Department of Medicine, Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom. j.m.king@bham.ac.uk
Brand
Oliver J
OJ
Barrett
Jeffrey C
JC
Carr-Smith
Jackie D
JD
Franklyn
Jayne A
JA
Gough
Stephen C
SC
D001172:Arthritis, Rheumatoid / Q000235:genetics; D016022:Case-Control Studies; D031885:Cimicifuga; D005192:Family Health; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases