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

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. Lay Summary What does this mean for patients? Interstitial lung disease (ILD), or non-infectious pneumonia, belongs to a class of lung diseases commonly characterized by thickening and scarring of tissue. ILD can lead to morbidity and mortality owing to problems with gas exchange between the lungs and the blood. Genetic polymorphisms, which are variations in DNA sequences between different people, might serve as a predictive marker of disease and help with faster diagnosis. A recent study reported that variations in the MUC5B gene were associated with ILD in rheumatoid arthritis patients worldwide. However, the genetic background was different among different populations. We tried to identify predictive markers of ILD in Japanese rheumatoid arthritis patients. We used a genome-wide association study to search for small variations in people's DNA. We found that a variation of the PPFIBP2 gene had the strongest association with ILD occurrence. Testing for this variation might help doctors to identify ILD occurrence before treatment for rheumatoid arthritis, which could improve patient outcomes.