RT Journal Article
SR Electronic
T1 Copy Number Variation of <em>HLA-DQA1</em> and <em>APOBEC3A/3B</em> Contribute to the Susceptibility of Systemic Sclerosis in the Chinese Han Population
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 880
OP 886
DO 10.3899/jrheum.150945
VO 43
IS 5
A1 Shicheng Guo
A1 Yuan Li
A1 Yi Wang
A1 Haiyan Chu
A1 Yulin Chen
A1 Qingmei Liu
A1 Gang Guo
A1 Wenzhen Tu
A1 Wenyu Wu
A1 Hejian Zou
A1 Li Yang
A1 Rong Xiao
A1 Yanyun Ma
A1 Feng Zhang
A1 Momiao Xiong
A1 Li Jin
A1 Xiaodong Zhou
A1 Jiucun Wang
YR 2016
UL http://www.jrheum.org/content/43/5/880.abstract
AB Objective. Systemic sclerosis (SSc) is a systemic connective tissue disease caused by a genetic aberrant. The involvement of the copy number variations (CNV) in the pathogenesis of SSc is unclear. We tried to identify some CNV that are involved with the susceptibility to SSc.Methods. A genome-wide CNV screening was performed in 20 patients with SSc. Five SSc-associated common CNV that included HLA-DRB5, HLA-DQA1, IRGM, CDC42EP3, and APOBEC3A/3B were identified from the screening and were then validated in 365 patients with SSc and 369 matched healthy controls.Results. Three hundred forty-four CNV (140 gains and 204 losses) and 2 CNV hotspots (6q21.3 and 22q11.2) were found in the SSc genomes (covering 24.2 megabases), suggesting that CNV were ubiquitous in the SSc genome and played important roles in the pathogenesis of SSc. The high copy number of HLA-DQA1 was a significantly protective factor for SSc (OR 0.07, p = 2.99 × 10−17), while the high copy number of APOBEC3A/B was a significant risk factor (OR 3.45, p = 6.4 × 10−18), adjusted with sex and age. The risk prediction model based on genetic factors in logistic regression showed moderate prediction ability, with area under the curve = 0.80 (95% CI 0.77–0.83), which demonstrated that APOBEC3A/B and HLA-DQA1 were powerful biomarkers for SSc risk evaluation and contributed to the susceptibility to SSc.Conclusion. CNV of HLA-DQA1 and APOBEC3A/B contribute to the susceptibility to SSc in a Chinese Han population.