Genetic association of htSNPs across the major histocompatibility complex with rheumatoid arthritis in an African-American population.
Notwithstanding the well-established association of HLA-DRB1 shared epitope alleles, interest remains in identifying additional major histocompatibility complex (MHC) region variants associated with rheumatoid arthritis (RA). We used a panel of 1201 haplotype-tagging single nucleotide polymorphisms (SNPs) designed for African Americans to find genetic variants associated with RA in a 3.8-Mb region encompassing the MHC. Conditioning on seven covariates, including HLA-DRB1 risk alleles and population structure, we identified an SNP in HLA-DOA (rs9276977) significantly associated with RA; minor allele frequency (MAF) 0.27 in cases versus 0.21 in controls, odds ratio (+/-95% confidence interval)=2.86 (1.61, 5.31). Genotyping of rs9276977 in an independent sample of African-American RA patients and controls did not replicate the association (MAF 0.28 in cases versus 0.27 in controls). This study points to the potential association of a SNP in the HLA-DOA gene with RA in African Americans, but also underscores the importance of replication of findings in larger patient cohorts.
Reynolds
R J
RJ
Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham (UAB), Birmingham, AL 35294-2182, USA.
Kelley
J M
JM
Hughes
L B
LB
Yi
N
N
Bridges
S L
SL
D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006681:HLA-D Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
D006681:HLA-D Antigens; C046148:HLA-DO antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains