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

ABSTRACT

Purpose

To investigate whether polymorphisms of GAS6 and PROS1, which each encode protein ligands for a family of tyrosine kinase receptors, are associated with Behçet’s disease (BD) in a Japanese population.

Methods

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 GAS6 and rs4857037 in PROS1.

Results

We 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.

Conclusions

Our 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.

KEYWORDS:

• Association study
• Behçet’s disease
• GAS6
• polymorphisms
• PROS1

Acknowledgments

We sincerely thank all of the study participants and all of the medical staff involved in the diagnoses and sample collection.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/09273948.2023.2173239

Additional information

Funding

This work was supported by the Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) KAKENHI [grant number 20K09830].