Association ofPTPN22Haplotypes with Graves’ Disease

Abstract

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.

Association between thyroid stimulating hormone receptor gene intron polymorphisms and autoimmune thyroid disease in a Chinese Han population

“…Correlation analyses between genotypes and clinical manifestations of GD or HT were separately investigated involving 1) the age of onset (≤30 years vs. ≥31 years [18,21]); 2) thyroid size (≤ I degree vs. ≥ II degree, goiter size is divided into three degrees by palpation: I degree, the goiter can not be seen but could be reached; II degree, the goiter can be seen and reached, but within the sternocleidomastoid; III degree, the goiter exceeds the exterior margin of sternocleidomastoid); 3) presence or absence of AITD family history (defined as the subjects' first-degree relatives including parents, children and siblings or second-degree relatives such as grandparents, uncles and aunts who had AITD occurrence); 4) presence or absence of ophthalmopathy (defined as a distinctive disorder characterized by inflammation and swelling of the extraocular muscles and orbital fat, eyelid retraction, periorbital edema, episcleral vascular injection, conjunctive swelling and proptosis).…”

“…Currently, several candidate genes have been reported, which include human leukocyte antigen (HLA) [4][5][6], cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) [7][8][9], thyroid stimulating hormone receptor (TSHR) [10][11][12][13][14], thyroglobulin (TG) [15,16], protein tyrosine phosphatase (PTPN) gene [17,18], CD40 gene [19,20] and FCRL3 gene [21]. Among these genes, TSHR is deemed to be an important autoantigen for thyroid and definitely plays a significant role in the pathogenesis of AITD [22].…”

PTPN22 Trp620 Explains the Association of Chromosome 1p13 With Type 1 Diabetes and Shows a Statistical Interaction With HLA Class II Genotypes

“…Heward et al (28) selected five common rheumatoid arthritis-associated SNPs to use as tag SNPs (rs2488458, rs12730735, rs1310182, rs1217413, and rs3811021) and reported no evidence of association with Graves' disease in 768 case subjects, 768 control subjects, and 313 families (minimum P ϭ 0.292). Using the five tag SNPs and rs2476601/Trp 620 , they did, however, obtain evidence for a predisposing haplotype (haplotype 2, P ϭ 6.77 ϫ 10 Ϫ8 ) and a protective haplotype (haplotype 3, P ϭ 3.7 ϫ 10 Ϫ5 ) (28). Dissection of the association of these haplotypes revealed that rs2476601/Trp 620 was responsible for the predisposing effect observed with haplotype 2 but could not explain the apparent protective effect obtained for haplotype 3 (28).…”

Follow-up of potential novel Graves' disease susceptibility loci, identified in the UK WTCCC genome-wide nonsynonymous SNP study

“…Tag SNPs in HDLBP and TEKT1, not originally typed in the nsSNP study also provide a weak signal for association in the complete geographically matched collection. A number of significant replicated associations have previously been reported for GD, the HLA class I and II regions, 9,10 cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), 11 protein tyrosine phosphatase non-receptor type 22 (PTPN22) 12,13 and TSHR 5 with ORs for the development of disease ranging from 1.50-3.00. Weaker replicated effects are also likely to be conferred by the interleukin 2 receptor alpha gene (IL2RA), 14 CD40 15,16 and FCRL 4 with lesser ORs of 1.10-1.30.…”