title: Association of hypoxia-inducible factor 1A (HIF1A) gene polymorphisms with systemic sclerosis in a French European Caucasian population.
abstract: OBJECTIVE
  Systemic 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  We observed an association between the HIF1A gene and SSc in a European Caucasian population, supporting a role for HIF1 in the pathophysiology of SSc.
authors.affiliation: René Descartes University, Department of Rheumatology A, Cochin Hospital, Paris.
authors.forename: J
authors.initials: J
authors.lastname: Wipff
authors.forename: P
authors.initials: P
authors.lastname: Dieude
authors.forename: J
authors.initials: J
authors.lastname: Avouac
authors.forename: K
authors.initials: K
authors.lastname: Tiev
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.forename: B
authors.initials: B
authors.lastname: Granel
authors.forename: E
authors.initials: E
authors.lastname: Diot
authors.forename: J
authors.initials: J
authors.lastname: Sibilia
authors.forename: L
authors.initials: L
authors.lastname: Mouthon
authors.forename: O
authors.initials: O
authors.lastname: Meyer
authors.forename: A
authors.initials: A
authors.lastname: Kahan
authors.forename: C
authors.initials: C
authors.lastname: Boileau
authors.forename: Y
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005602:France / Q000453:epidemiology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011336:Probability; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit