Association between a stromal cell-derived factor 1 (SDF-1/CXCL12) gene polymorphism and microvascular disease in systemic sclerosis

Ann Rheum Dis. 2009 Mar;68(3):408-11. doi: 10.1136/ard.2008.098277. Epub 2008 Oct 17.

Abstract

Objective: To investigate the possible implication of SDF1-3' polymorphism in systemic sclerosis (SSc) susceptibility or clinical phenotype, or both.

Methods: 150 patients with SSc and 150 controls were enrolled. Skin involvement, autoantibodies, interstitial lung disease, pulmonary arterial hypertension (PAH), scleroderma renal crisis, 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 than in SSc-non-PAH (33.3% vs 18.3%, p = 0.01) and in SSc with skin ulcers than in SSc without ulcers (27.3% vs 16.9%, p = 0.03). The SDF1-3'A allele influenced the predisposition to SSc-related PAH (OR = 2.52, 95% CI 1.11 to 5.69, p = 0.02) and skin ulcers (OR = 2.31, 95% CI 1.18 to 4.52, p = 0.01). After adjustment for age and gender, the SDF1-3'A allele remained a susceptibility factor for the SSc-related vascular manifestations (PAH: OR = 2.37, 95% CI 1.04 to 5.42, p = 0.04; ulcers: OR = 2.33, 95% CI 1.78 to 4.62, p = 0.01).

Conclusion: The SDF1-3'A allele is significantly associated with microvascular involvement in SSc.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood
  • Chemokine CXCL12 / genetics*
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Microvessels
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction / methods
  • Polymorphism, Restriction Fragment Length
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology
  • Skin Ulcer / etiology*
  • Skin Ulcer / genetics

Substances

  • Autoantibodies
  • Chemokine CXCL12