Objective: Systemic sclerosis (SSc) is characterised by generalised microangiopathy with defective angiogenesis and vasculogenesis. SDF-1/CXCL12 and its receptor CXCR4 play crucial roles in angiogenesis and EPC mobilization/homing to ischemic tissues. Perturbation of SDF-1/CXCR4 axis was implicated in the pathogenesis of SSc-related microvasculopathy. A SDF-1 gene polymorphism (SDF1-3') was associated with SDF-1 expression and CD34+ progenitor cell mobilization. We investigated the possible implication of SDF1-3' polymorphism in SSc susceptibility and/or clinical phenotype.
Methods: 150 SSc patients and 150 controls were enrolled. Skin involvement, autoantibodies, ILD, PAH, SRC, past and/or current skin ulcers were assessed. Genotyping was performed by PCR-RFLP.
Results: Genotype distribution and allele frequency were similar in SSc and controls. SDF1-3'A allele and SDF1-3'GA/AA genotype frequencies were significantly higher in SSc-PAH compared with SSc-nonPAH (P=0.01), and in SSc with skin ulcers compared with SSc without ulcers (P=0.03). SDF1-3'A allele influenced the predisposition to SSc-related PAH (OR 2.52, 95%CI 1.11–5.69, P=0.02), and skin ulcers (OR 2.31, 95%CI 1.18–4.52, P=0.01). After adjustment for age and gender, SDF1-3'A allele remained a susceptibility factor for the SSc-related vascular manifestations (for PAH, OR 2.37, 95%CI 1.04–5.42, P=0.04; for ulcers, OR 2.33, 95%CI 1.78–4.62, P=0.01).
Conclusion: SDF1-3'A allele is significantly associated with microvascular involvement in SSc.
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