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.
Keywords: CASE-CONTROL STUDIES; COPY NUMBER VARIATION; GENETIC PREDISPOSITION TO DISEASE; HLA ANTIGENS; SYSTEMIC SCLEROSIS.