Replication Study of the Association of <i>GAS6</i> and <i>PROS1</i> Polymorphisms with Behçet’s Disease in a Japanese Population

To investigate whether polymorphisms of <i>GAS6</i> and <i>PROS1</i>, which each encode protein ligands for a family of tyrosine kinase receptors, are associated with Behçet’s disease (BD) in a Japanese population. We 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 <i>GAS6</i> and rs4857037 in <i>PROS1</i>. We found that <i>GAS6</i> rs9577873 was not significantly associated with BD. In contrast, <i>PROS1</i> 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 <i>PROS1</i> expression. Our findings suggest that increased <i>PROS1</i> expression related to the A risk allele of rs4857037 affects tyrosine kinase receptor signaling, contributing to the development of BD.