An allograft inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is associated with anticentromere antibody positive systemic sclerosis |
| |
Authors: | Alkassab F Gourh P Tan F K McNearney T Fischbach M Ahn C Arnett F C Mayes M D |
| |
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 |
| |
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. 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. |
| |
Keywords: | |
本文献已被 PubMed Oxford 等数据库收录! |
|