Abstract
Objective. To determine whether angiotensin-converting enzyme (ACE) polymorphisms including I/D and 2 single-nucleotide polymorphisms (SNP) affect susceptibility to systemic sclerosis (SSc) in a large French Caucasian population.
Methods. A case-control study was performed in 494 patients with SSc and 280 healthy controls for I/D polymorphism. Two supplementary exonic SNP of ACE gene (rs4309, rs4362) were genotyped in 659 patients with SSc and 511 matched healthy controls. Among the whole SSc population, 453 (67%) patients with SSc had the limited cutaneous subtype, 47 (7%) had precapillary pulmonary arterial hypertension, 209 (32%) had digital ulcers, and 10 (1.5%) had renal crisis. A combined analysis of the available results for ACE I/D genotypes in Caucasians was also performed.
Results. There was no association between the 3 polymorphic markers and SSc for allelic and genotype frequencies. No association was observed for the different vascular subsets of the disease. Haplotype analyses did not detect any association. The lack of association for ACE I/D was confirmed by the combined analysis.
Conclusion. These results in a large cohort of European Caucasian patients with SSc do not support that the ACE gene is implicated in the pathogenesis of SSc and its vascular damage.
Footnotes
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Supported by Association des Sclérodermiques de France, Société Française de Rhumatologie, INSERM, and Agence Nationale pour la Recherche (grant R07094KS) and by Groupe Français de Recherche sur la Sclérodermie.
- Accepted for publication September 15, 2008.