Objective: To evaluate the role of the single-nucleotide polymorphism (SNP) at position -670 in the FAS gene promoter (FAS-670G>A) in influencing the susceptibility, the clinical features and the severity of systemic sclerosis (SSc).
Methods: We studied 350 Italian Caucasian SSc patients (259 with limited cutaneous SSc [lcSSc] and 91 with diffuse cutaneous SSc [dcSSc]) and 232 healthy subjects. Patients were assessed for the presence of autoantibodies (anticentromere, anti-topoisomerase I [anti-Scl-70] antibodies), interstitial lung disease (ILD), pulmonary arterial hypertension and scleroderma renal crisis. FAS-670G>A SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum levels of soluble FAS were analysed by ELISA.
Results: A significant difference in FAS-670 genotype distribution was observed between SSc patients and healthy subjects (P=0.0012). The frequency of FAS-670A allele was significantly higher in SSc than in controls (P=0.0004). No significant difference in genotype distribution and allele frequencies was observed between lcSSc and dcSSc, although a higher frequency of FAS-670A allele in dcSSc was found. FAS-670AA genotype significantly influenced the predisposition to SSc (OR 1.97, 95%CI 1.35-2.88, P=0.0004), and to both lcSSc (OR 1.84, 95%CI 1.23-2.75, P=0.003) and dcSSc (OR 2.37, 95%CI 1.41-3.99, P=0.001). FAS-670A allele frequency was higher, although not significantly, in anti-Scl-70 antibody-positive dcSSc and in ILD dcSSc. Soluble FAS was significantly higher in patients and controls carrying FAS-670AA genotype compared with those carrying FAS-670GG genotype (P=0.003).
Conclusion: The FAS-670A allele is significantly associated with susceptibility to SSc, suggesting a role for a genetic control of apoptosis in the pathogenesis of the disease.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.