Exp Mol Med.
2011 Nov;43(11):613-621. 10.3858/emm.2011.43.11.068.
Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis
- Affiliations
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- 1Integrated Research Center for Genome Polymorphism, The Catholic University of Korea School of Medicine, Seoul 137-701, Korea. yejun@catholic.ac.kr
- 2Department of Microbiology, The Catholic University of Korea School of Medicine, Seoul 137-701, Korea.
- 3Genome Research Center for Immune Disorders, School of Medicine, Wonkwang University, Iksan 570-749, Korea.
- 4Department of Medical Humanities and Social Sciences, The Catholic University of Korea School of Medicine, Seoul 137-701, Korea.
- 5Department of Internal Medicine, The Catholic University of Korea School of Medicine, Seoul 137-701, Korea.
- 6Division of Rheumatology, Department of Internal Medicine, Eulji Medi-Bio Research Institute, Eulji University School of Medicine, Daejeon 301-746, Korea.
- KMID: 1025164
- DOI: http://doi.org/10.3858/emm.2011.43.11.068
Abstract
- Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 x 10(-7)). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 x 10(-5)). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 +/- 10(-10)). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.
Keyword
MeSH Terms
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Apolipoproteins/*genetics
Arthritis, Rheumatoid/*genetics
Case-Control Studies
DNA/genetics
Female
*Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Heterozygote
Homozygote
Humans
Lipocalins/*genetics
Luciferases/metabolism
Male
Middle Aged
Polymorphism, Single Nucleotide/*genetics
Promoter Regions, Genetic/*genetics
Real-Time Polymerase Chain Reaction
Risk Factors
