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ORIGINAL ARTICLE

Positive association of genetic variations in the phospholipase C-like 1 gene with dermatomyositis in Chinese Han Qian Wang1 • Si Chen1 • Yuan Li1 • Ping Li1 • Chanyuan Wu1 • Ziyan Wu1 Qingjun Wu1 • Fei Sun1 • Jing Li1 • Wenjie Zheng1 • Chuiwen Deng1 • Fengchun Zhang1 • Yongzhe Li1

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Ó Springer Science+Business Media New York 2015

Abstract Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases with an underlying yet undefined genetic component. Recently, phospholipase C-like 1 (PLCL1) has been identified as a potential genetic susceptibility locus for dermatomyositis (DM) in patients of European ancestry. Here, association between PLCL1 polymorphisms and IIMs was investigated in Chinese Han. Genomic DNA was isolated from blood samples (2 mL) collected from Chinese Han (C18 years) with polymyositis (PM, n = 286) or dermatomyositis (DM, n = 535) and ethnically matched controls (n = 968). Patients and controls were genotyped for five SNPs (rs938929, rs1518364, rs6738825, rs2117339, and rs7572733) previously associated with DM, with the Sequenom MassARRAY system. SNPs rs6738825 and rs7572733 were found to be associated with the development of DM in Chinese Han (Pc = 0.015; Pc = 0.025, respectively) as well as the risk A allele of rs938929 and T allele of rs1518364 (Pc = 0.030; Pc = 0.029). None of the five SNPs were associated with PM (all Pc [ 0.05). The frequency of the

Qian Wang, Si Chen, and Yuan Li have contributed equally to this manuscript.

Electronic supplementary material The online version of this article (doi:10.1007/s12026-015-8738-x) contains supplementary material, which is available to authorized users. & Yongzhe Li [email protected] 1

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, 41 Damucang Hutong, Xicheng District, Beijing 100032, China

two haplotypes of these five SNPs was also significantly different between DM patients and healthy controls. In addition, conditional analysis with rs6738825 revealed that these SNPs were not independent factors contributing to DM. Finally, a novel association between rs6738825 and rs7572733 and DM with complicating interstitial lung disease was observed (ILD; Pc = 0.040; Pc = 0.030, respectively). A positive association between PLCL1 polymorphisms and DM patients and DM patients with ILD was observed, indicating that PLCL1 might be the susceptibility gene for DM patients in Chinese Han. Keywords Dermatomyositis  Polymyositis  Phospholipase C-like 1 gene  Polymorphism  Association

Introduction The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases affecting skeletal muscles. They are primarily characterized by symmetric, proximal muscle weakness, muscle enzyme elevations, inflammatory cell infiltrates in muscle biopsy specimens, and electromyographic abnormalities on neurophysiological tes