Identification of novel genetic susceptibility loci for Behçet's disease using a genome-wide association study.
BACKGROUND
Behçet's disease is a chronic systemic inflammatory disease that remains incompletely understood. Herein, we perform the first genome-wide association study in Behçet's disease.


METHODS
Using DNA pooling technology and the Affymetrix 500K arrays, we identified possible candidate gene associations with Behçet's disease in a cohort of 152 Behçet's disease patients and 172 healthy ethnically matched controls. Genetic loci that were identified in the pooling study were genotyped in patients and controls using TaqMan genotyping technology.


RESULTS
We identified genetic associations between Behçet's disease and single-nucleotide polymorphisms (SNPs) in KIAA1529, CPVL, LOC100129342, UBASH3B, and UBAC2 (odds ratio = 2.04, 2.26, 1.84, 1.71, and 1.61, respectively; P value = 4.2 x 10-5, 1.0 x 10-4, 3.0 x 10-4, 1.5 x 10-3, and 5.8 x 10-3, respectively). Among the associated SNPs, the Behçet's disease-risk allele in rs2061634 leads to substitution of serine to cysteine at amino acid position 995 (S995C) in the KIAA1529 protein.


CONCLUSIONS
Using an unbiased whole-genome genetic association approach, we identified novel candidate genetic loci that are associated with increased susceptibility for Behçet's disease. These findings will help to better understand the pathogenesis of Behçet's disease and identify novel targets for therapeutic intervention.
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. yiping-fei@omrf.org
Yiping
Y
Fei
Ryan
R
Webb
Beth L
BL
Cobb
Haner
H
Direskeneli
Güher
G
Saruhan-Direskeneli
Amr H
AH
Sawalha
D000328:Adult; D001528:Behcet Syndrome / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D055815:Young Adult