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We appreciate the comments by Bluett et al 1 on our report of an association of HLA-A*31:01 with methotrexate-induced interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).2 They have tried to reveal the genetic factors associated with methotrexate-induced ILD, but found no significant association except three suggestive loci in chromosome 1, 9 and 14. This study did not show the association of A*31:01 with methotrexate-induced ILD, though the p value of the analysis was still 0.21 in spite of the small sample size with 62 cases and 175 controls. The meta-analysis with our previous study2 or other forthcoming HLA association studies on methotrexate-induced ILD may reveal more conclusive results in the future.
Genetic factors would be involved in the pathogenesis of methotrexate-induced ILD, because the susceptibility of methotrexate-induced ILD in Japanese patients with RA are thought to be higher than other ethnic groups or patients with other autoimmune diseases.3 4 However, there are few reports of genome-wide association study of drug-induced ILD.5 Since the prevalence of drug-induced ILD is low and the clinical conditions of the patients with drug-induced ILD are various,6 genetic analyses …