An allograft inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is associated with anticentromere antibody positive systemic sclerosis
F Alkassab, P Gourh, FK Tan, T McNearney… - …, 2007 - academic.oup.com
F Alkassab, P Gourh, FK Tan, T McNearney, M Fischbach, C Ahn, FC Arnett, MD Mayes
Rheumatology, 2007•academic.oup.comObjective. 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 …
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 …
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.
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