L-selectin gene polymorphisms in Graves' disease.

OBJECTIVE

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. There is strong evidence that members of the selectin family participate in the interaction between leucocytes and the endothelium, as well as in inflammatory cell recruitment. Moreover, a high serum level of a soluble form of L-selectin (SL-selectin) has been reported in untreated GD patients. However, the impact of L-selectin polymorphisms on GD has not yet been investigated. The aim of the present study was to elucidate whether L-selectin gene polymorphisms were associated with the development of GD.

SUBJECTS AND DESIGN

L-selectin gene polymorphisms were investigated in 230 Chinese GD patients and 208 healthy control subjects without antithyroid autoantibodies or a family history of autoimmune disorders. Two L-selectin SNPs were genotyped by the PCR-restriction fragment length polymorphism (PCR-RFLP) method.

RESULTS

A C/T polymorphism at position -642 of the promoter region and a Pro213Ser (c.725 C-T) polymorphism in exon 6 were examined using PCR-RFLP. There was a significant increase in -642T allele frequency in GD patients compared with healthy controls (70 vs. 62%; P = 0.0126; P(c) = 0.0252). The frequency of the c.725C allele in exon 6 also appeared higher in GD patients than in controls. Haplotype analysis showed a significant decrease in the -642C/c.725T haplotype in GD patients (26 vs. 34%; P = 0.0095; Pc = 0.0190). However there was no association between polymorphisms and certain GD clinical phenotypes, including age of onset and ophthalmopathy.

CONCLUSIONS

L-selectin gene polymorphisms are associated with GD susceptibility in Chinese patients.