A genome-wide association study identifying single nucleotide polymorphisms in the PPFIBP2 gene was predictive for interstitial lung disease in rheumatoid arthritis patients

Shinya Hayashi; Tsukasa Matsubara; Koji Fukuda; Toshihisa Maeda; Keiko Funahashi; Marowa Hashimoto; Yoshinori Takashima; Kenichi Kikuchi; Masahiro Fujita; Tomoyuki Matsumoto; Ryosuke Kuroda

doi:10.1093/rap/rkac088

A genome-wide association study identifying single nucleotide polymorphisms in the PPFIBP2 gene was predictive for interstitial lung disease in rheumatoid arthritis patients

Rheumatol Adv Pract. 2022 Oct 29;6(3):rkac088. doi: 10.1093/rap/rkac088. eCollection 2022.

Affiliations

¹ Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
² Department of Orthopaedic Surgery, Matsubara Mayflower Hospital, Kato, Japan.
³ Research Institute of Joint Diseases, Kobe, Japan.

Abstract

Objective: Genetic polymorphisms might serve as useful prognostic markers for the timely diagnosis of RA. The purpose of this study was to identify genomic factors predictive of the occurrence of interstitial lung disease (ILD) in RA by performing a genome-wide association study of genetic variants, including single nucleotide polymorphisms (SNPs).

Methods: The study population included 306 RA patients. All patients were treated with conventional DMARDs, including 6-16 mg MTX per week. Clinical data and venous blood samples were collected from all patients before administration of DMARDs. A total of 278 347 SNPs were analysed to determine their association with ILD occurrence.

Results: Several SNPs were strongly associated with ILD occurrence (P < 10^-5). rs6578890, which is located on chromosome 11 in the intronic region of the gene encoding tyrosine phosphatase receptor type F polypeptide-interacting protein-binding protein 2 (PPFIBP2), showed the strongest association with ILD occurrence (odds ratio 4.32, P = 10^-7.93).

Conclusion: PPFIBP2 could be a useful genetic marker for occurrence of interstitial pneumonia in RA patients and might help to identify the risk of ILD occurrence before RA treatment, thereby improving patient outcomes.

Keywords: PPFIBP2; RA; genome-wide screening; interstitial lung disease; single nucleotide polymorphisms.