title: An allograft inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is associated with anticentromere antibody positive systemic sclerosis.
abstract: OBJECTIVE
  To identify genetic associations between allograft inflammatory factor 1 (AIF1) and systemic sclerosis (SSc), or its subsets, using a single nucleotide polymorphism (SNP) in a replicate case-control study.
  
  
  METHODS
  The frequencies of alleles and genotypes of an SNP, rs2269475, for the AIF1 gene were examined in two large independent cohorts of SSc patients (n = 1015 total), and compared with two groups of normal controls (n = 893 total). Both cases and controls were stratified by ethnicity (Caucasian, African American and Hispanic) and by autoantibody status [anti-centromere antibodies (ACA) and anti-topoisomerase I antibody (ATA)].
  
  
  RESULTS
  The minor T allele and CT/TT genotype frequencies of the AIF1 SNP were not observed more frequently in SSc patients of the three ethnic groups (individually or combined) when compared with controls. On the other hand, T and CT/TT frequencies were significantly increased in ACA-positive Caucasian SSc patients, and all ACA-positive SSc patients (the three ethnic groups combined), when compared with ACA-negative SSc patients and with normal controls, with odds ratios of approximately 1.5.
  
  
  CONCLUSIONS
  The data demonstrate a genetic association between AIF1 and the ACA-positive subset of SSc. This polymorphism is a non-synonymous substitution and therefore likely to represent an important functional change in AIF1. Since vascular pathology is a prominent feature in ACA-positive SSc patients, the observed association with a vasculotrophic inflammatory gene is biologically plausible and warrants further research.
authors.affiliation: Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Health Science Center at Houston (UTH), Houston, TX 77030, USA. firas.alkassab@uth.tmc.edu
authors.forename: F
authors.initials: F
authors.lastname: Alkassab
authors.forename: P
authors.initials: P
authors.lastname: Gourh
authors.forename: F K
authors.initials: FK
authors.lastname: Tan
authors.forename: T
authors.initials: T
authors.lastname: McNearney
authors.forename: M
authors.initials: M
authors.lastname: Fischbach
authors.forename: C
authors.initials: C
authors.lastname: Ahn
authors.forename: F C
authors.initials: FC
authors.lastname: Arnett
authors.forename: M D
authors.initials: MD
authors.lastname: Mayes
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood*; D002135:Calcium-Binding Proteins; D002503:Centromere / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004812:Epidemiologic Methods; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008840:Microfilament Proteins; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D014481:United States / Q000453:epidemiology
chemical_list: C112986:AIF1 protein, human; D000974:Antibodies, Antinuclear; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins