Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis.
10.3858/emm.2011.43.11.068
- Author:
Hae Jin HU
1
;
Eun Heui JIN
;
Seon Hee YIM
;
So Young YANG
;
Seung Hyun JUNG
;
Seung Hun SHIN
;
Wan Uk KIM
;
Seung Cheol SHIM
;
Tai Gyu KIM
;
Yeun Jun CHUNG
Author Information
1. Integrated Research Center for Genome Polymorphism, The Catholic University of Korea School of Medicine, Seoul 137-701, Korea. yejun@catholic.ac.kr
- Publication Type:Original Article ; Comparative Study
- Keywords:
APOM protein, human;
autoimmune diseases;
genome-wide association study;
polymorphism, single nucleotide;
rheumatoid arthritis
- MeSH:
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
- From:Experimental & Molecular Medicine
2011;43(11):613-621
- CountryRepublic of Korea
- Language:English
-
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.
