The FAS −670A>G polymorphism influences susceptibility to systemic sclerosis phenotypes
Article first published online: 30 NOV 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 12, pages 3815–3820, December 2009
How to Cite
Broen, J., Gourh, P., Rueda, B., Coenen, M., Mayes, M., Martin, J., Arnett, F. C. and Radstake, T. R. D. J. (2009), The FAS −670A>G polymorphism influences susceptibility to systemic sclerosis phenotypes. Arthritis & Rheumatism, 60: 3815–3820. doi: 10.1002/art.24964
- Issue published online: 30 NOV 2009
- Article first published online: 30 NOV 2009
- Manuscript Accepted: 10 AUG 2009
- Manuscript Received: 3 APR 2009
- I3P CSIC program funded by the Fondo Social Europeo
- NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Scleroderma Registry and DNA Repository. Grant Number: N01-AR-0-2251
- Spanish Ministry of Science and Innovation. Grant Number: SAF2009-11110
- Andalusian Ministry of Science and Innovation. Grant Number: CTS-1180
- Genetica Fundación Española de Reumatología
- NIH/NIAMS Center of Research Translation in Scleroderma. Grant Number: 1-P50-AR-054144
- Center of Clinical and Translational Sciences (Houston Clinical and Translational Science Award Program). Grant Number: 1-U54-RR-23417
- VIDI laureate from the Netherlands Organization for Scientific Research
To investigate the possible role of the FAS −670A>G functional polymorphism in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype.
A total of 2,900 SSc patients and 3,186 healthy controls were included in this study. We analyzed the genotype and allele frequencies of the FAS −670A>G polymorphism in 9 distinct ethnic cohorts, including 6 cohorts of European ancestry (a Spanish cohort of 228 SSc patients and 265 controls, a Dutch cohort of 203 SSc patients and 277 controls, a German cohort of 313 SSc patients and 247 controls, an Italian cohort of 323 SSc cases and 89 controls, a British cohort of 269 SSc patients, and a Swedish cohort of 182 patients) and 3 distinct ethnic cohorts from the US (a cohort of 1,047 white patients and 692 controls, a cohort of 159 Hispanic patients and 137 controls, and a cohort of 176 black SSc patients and 194 controls). Genotyping was performed using a TaqMan 5′ allelic discrimination assay.
In the British, Italian, and American white cohorts we observed an association of the FAS −670G allele with limited cutaneous SSc (lcSSc) (odds ratios [ORs] 1.25, 1.43, and 1.18, respectively). A meta-analysis comprising all 9 cohorts revealed an association of both the FAS −670G allele (OR 1.10) and the FAS −670GG genotype (OR 1.13) with the lcSSc phenotype. In a meta-analysis including only white subjects, both the FAS −670G allele and the FAS −670GG genotype remained associated with lcSSc (allele OR 1.12; genotype OR 1.16). In addition, a recessive model of the −670GG genotype exhibited a strong association with SSc, lcSSc, and anticentromere antibody–positive lcSSc (OR 1.23, OR 1.33, and OR 1.45, respectively).
Our data show that the FAS −670A>G polymorphism plays a role in lcSSc susceptibility. A similar trend has been observed in other autoimmune diseases.