title: Polymorphisms in COL15 gene are not associated with systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is marked by microvascular abnormalities leading to ischemic features such as Raynaud's phenomenon and fingertip ulcers. Digital ischemia in turn results in hypoxia, which is expected to drive compensatory angiogenesis; however, this phenomenon is deregulated in SSc. Vascular basement membrane (VBM) that consists of type IV, XV, and XVIII collagens supports the growth and survival of vascular endothelial cells and plays a key role in regulating angiogenesis. Recent gene expression analyses of skin tissue and dermal fibroblasts from patients with SSc revealed COL15 to be one of the significantly differentially regulated genes. We undertook an association study to explore the role of COL15 single-nucleotide polymorphisms (SNP) in SSc disease development.
  
  
  METHODS
  Eleven SNP across COL15 were genotyped in a cohort of 175 UK Caucasian patients with SSc and 190 population-matched unrelated healthy subjects using 2 methods: TaqMan and SNaPshot. Statistical analysis was performed by Pearson's chi-square test and HelixTree software was utilized for haplotype analysis.
  
  
  RESULTS
  No difference in genotype or allele frequencies were detected between patients with SSc and controls. None of the haplotype frequencies were found to differ between patients and controls.
  
  
  CONCLUSIONS
  Failure to detect an association may reflect a true lack of association or could be a false-negative result arising as a result of low power of the study. Our study had sufficient power to detect an effect size of 2.1 (p = 0.05); however, larger patient cohorts may be needed for exclusion of COL15 from a possible candidacy in SSc.
authors.affiliation: National Genetics Reference Laboratory, Department of Medical Genetics, St. Mary's Hospital, Hathersage Road, Manchester M13 0JH, UK. sudeep.parameshwar@cmmc.nhs.uk
authors.forename: Sudeep P
authors.initials: SP
authors.lastname: Pushpakom
authors.forename: Ariane L
authors.initials: AL
authors.lastname: Herrick
authors.forename: Shant
authors.initials: S
authors.lastname: Kumar
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
mesh_terms: D016022:Case-Control Studies; D003094:Collagen / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012595:Scleroderma, Systemic / Q000235:genetics*
chemical_list: C085811:COL15A1 protein, human; D003094:Collagen