Replication Study of the Association of GAS6 and PROS1 Polymorphisms with Behcet's Disease in a Japanese Population

PurposeTo investigate whether polymorphisms of GAS6 and PROS1, which each encode protein ligands for a family of tyrosine kinase receptors, are associated with Behcet's disease (BD) in a Japanese population.MethodsWe recruited 734 Japanese patients with BD and 1789 Japanese healthy controls. In all participants, we genotyped two single-nucleotide polymorphisms (SNPs) reportedly associated with BD: rs9577873 in GAS6 and rs4857037 in PROS1.ResultsWe found that GAS6 rs9577873 was not significantly associated with BD. In contrast, PROS1 rs4857037, specifically the A allele, was associated with increased risk for BD. The A allele was also significantly associated with BD under additive and recessive genetic models. Expression analysis revealed that this allele was significantly associated with increased PROS1 expression.ConclusionsOur findings suggest that increased PROS1 expression related to the A risk allele of rs4857037 affects tyrosine kinase receptor signaling, contributing to the development of BD.

Automated summary

The study aimed to investigate the association between polymorphisms of GAS6 and PROS1 and Behcet's disease (BD) in a Japanese population. Genetic analysis was conducted on 734 Japanese patients with BD and 1789 healthy controls. The results showed that GAS6 rs9577873 was not significantly associated with BD, whereas PROS1 rs4857037 (particularly the A allele) was associated with increased risk of BD. Expression analysis revealed that the A risk allele was associated with upregulated PROS1 expression. These findings suggest that increased PROS1 expression contributes to the development of BD by affecting tyrosine kinase receptor signaling.