Positive association of genetic variations in the phospholipase C-like 1 gene with dermatomyositis in Chinese Han
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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 (≥18 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 (P c = 0.015; P c = 0.025, respectively) as well as the risk A allele of rs938929 and T allele of rs1518364 (P c = 0.030; P c = 0.029). None of the five SNPs were associated with PM (all P c > 0.05). The frequency of the 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; P c = 0.040; P c = 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.
KeywordsDermatomyositis Polymyositis Phospholipase C-like 1 gene Polymorphism Association
We would like to give our sincere appreciation and thanks to all the patients with PM/DM, who made this study possible, to Chunwei Cao for the useful suggestion he offered, and to Yang Du for the expertise and technical assistance.
This work was supported by funding from the Research Special Fund for Public Welfare Industry of Health (201202004), and the National Natural Science Foundation of China Grants (81172857, 81373188), the Chinese National High Technology Research and Development Program, Ministry of Science and Technology Grants (2011AA02A113), the National Science Technology Pillar Program in the 12th Five-year Plan (2014BAI07B00), and the Capital Health Research and Development of Special (2014-1-4011).
Compliance with ethical standards
The study was approved by the Ethics Committee of the Peking Union Medical College Hospital.
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in the study.
- 12.Gono T, Kawaguchi Y, Kuwana M, Sugiura T, Furuya T, Takagi K, et al. Brief report: association of HLA-DRB1*0101/*0405 with susceptibility to anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis in the Japanese population. Arthritis Rheumatol. 2012;64:3736–40.CrossRefGoogle Scholar
- 15.Pachman LM, Liotta-Davis MR, Hong DK, Kinsella TR, Mendez EP, Kinder JM, et al. TNFalpha-308A allele in juvenile dermatomyositis: association with increased production of tumor necrosis factor alpha, disease duration, and pathologic calcifications. Arthritis Rheumatol. 2000;43:2368–77.CrossRefGoogle Scholar
- 23.Chinoy H, Platt H, Lamb JA, Betteridge Z, Gunawardena H, Fertig N, et al. The protein tyrosine phosphatase N22 gene is associated with juvenile and adult idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype in British Caucasian patients. Arthritis Rheumatol. 2008;58:3247–54.CrossRefGoogle Scholar