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 ∼1.5. Conclusion. 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.
Original language | English (US) |
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Pages (from-to) | 1248-1251 |
Number of pages | 4 |
Journal | Rheumatology |
Volume | 46 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2007 |
Keywords
- AIF1
- Allograft inflammatory factor 1
- Anticentromere antibodies
- Autoantibodies
- Genetics
- Scleroderma
- Systemic sclerosis
ASJC Scopus subject areas
- Rheumatology
- Pharmacology (medical)