WDFY4 polymorphisms in Chinese patients with anti-MDA5 dermatomyositis is associated with rapid progressive interstitial lung disease.

Objectives Anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis (MDA5 + DM), is susceptible to development of rapidly progressive interstitial lung disease (RPILD), which has been predominantly reported in East Asia. A Japanese genome-wide study has identified a WDFY4 variant rs7919656 linkage. We sought to evaluate this genetic marker and exploit its possible clinical relevance in Chinese MDA5 + DM. Methods We genotyped and compared the minor allele A frequency of WDFY4 rs7919656 in patients with MDA5 + DM (n  = 254) including 190 clinically amyopathic dermatomyositis (CADM), MDA5 - DM (n  = 53), anti-synthetases syndrome (ASyS, n  = 72) and healthy controls (n  = 192). Association of the WDFY4 variant with clinical phenotype was evaluated using logistic regression. Results Although the minor allele A frequencies of WDFY4 rs7919656 in MDA5 + DM and CADM were comparable to that in healthy controls, we observed a significant correlation between the WDFY4 variant (GA+AA genotype) and the incidence of RPILD in MDA5 + DM (OR: 2.11; 95% CI: 1.21, 3.69; P  = 0.007). Moreover, this variant was an independent risk factor for RPILD in multivariate analysis (OR: 4.98; 95% CI: 1.59, 17.19; P  = 0.008), along with other well-recognized risk factors, i.e. forced vital capacity % predicted, diffusing capacity for carbon monoxide % predicted, serum ferritin and prednisolone exposure. In addition, this variant was associated with higher expression of WDFY4 in PBMCs of MDA5 + DM, especially those with RPILD. WDFY4 overexpression was also observed in lung biopsy of MDA5 + DM-RPILD bearing the variant genotype. Conclusion We found that the WDFY4 variant was associated with an increased risk of RPILD, not with disease susceptibility in Chinese MDA5 + DM. [ABSTRACT FROM AUTHOR]

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