• J Wipff, P Dieude, J Avouac, K Tiev, E Hachulla, B Granel, E Diot, J Sibilia, L Mouthon, O Meyer, A Kahan, C Boileau, and Y Allanore.
• René Descartes University, Department of Rheumatology A, Cochin Hospital, Paris.
• Scand. J. Rheumatol. 2009 Jan 1;38(4):291-4.

ObjectiveSystemic sclerosis (SSc) is a connective tissue disease characterized by generalized microangiopathy leading to chronic hypoxia. The aim of this study was to determine whether polymorphisms of the hypoxia-inducible factor 1A gene (HIF1A) affects susceptibility to SSc in a large French European Caucasian population.MethodsA case-control study was performed in 659 SSc patients and 511 healthy matched controls. Three tag single nucleotide polymorphisms (SNPs) of the HIF1A gene (rs12434438 A/G, rs1957757 C/T, and rs11549465 C/T) were genotyped allowing whole gene coverage according to HapMap data.ResultsThe frequency of genotypes carrying at least one G allele (A/G and/or GG) of the rs12434438 SNP was significantly higher in SSc patients than in controls [p(corr) = 0.018, odds ratio (OR) 1.44, 95% confidence interval (CI) 1.08-1.91]. Regarding SSc subgroup analyses, the heterozygous genotype A/G was associated with SSc (p(corr) = 0.012, OR 1.47, 95% CI 1.13-1.9), with the limited cutaneous form of SSc (p(corr) = 0.04, OR 1.43, 95% CI 1.08-1.91), and with positive anti-centromere antibodies (ACA; p(corr) = 0.016, OR 1.61, 95% CI 1.16-2.23). No association was detected for the remaining two HIF1A SNPs tested. Haplotype analyses did not detect any association with SSc.ConclusionsWe observed an association between the HIF1A gene and SSc in a European Caucasian population, supporting a role for HIF1 in the pathophysiology of SSc.

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