Identification of multiple genetic susceptibility loci in Takayasu arteritis.
Am J Hum Genet
; 93(2): 298-305, 2013 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-23830517
ABSTRACT
Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2) HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arterite de Takayasu
/
Predisposição Genética para Doença
/
Loci Gênicos
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
America do norte
/
Asia
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article