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. 2009 Dec;60(12):3815-20.
doi: 10.1002/art.24964.

The FAS -670A>G polymorphism influences susceptibility to systemic sclerosis phenotypes

J Broen  1 , P Gourh, B Rueda, M Coenen, M Mayes, J Martin, F C Arnett, T R D J Radstake; European Consortium on Systemic Sclerosis Genetics
Collaborators, Affiliations

The FAS -670A>G polymorphism influences susceptibility to systemic sclerosis phenotypes

J Broen et al. Arthritis Rheum. 2009 Dec.

Abstract

Objective: To investigate the possible role of the FAS -670A>G functional polymorphism in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype.

Methods: 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.

Results: 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).

Conclusion: 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.

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