title: Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis.
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 × 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 × 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.
authors.affiliation: Integrated Research Center for Genome Polymorphism, The Catholic University of Korea School of Medicine Seoul 137-701, Korea.
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Hu
authors.forename: Eun Heui
authors.initials: EH
authors.lastname: Jin
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Yim
authors.forename: So Young
authors.initials: SY
authors.lastname: Yang
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Jung
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Shin
authors.forename: Wan Uk
authors.initials: WU
authors.lastname: Kim
authors.forename: Seung Cheol
authors.initials: SC
authors.lastname: Shim
authors.forename: Tai Gyu
authors.initials: TG
authors.lastname: Kim
authors.forename: Yeun Jun
authors.initials: YJ
authors.lastname: Chung
mesh_terms: D001053:Apolipoproteins / Q000235:genetics*; D000075243:Apolipoproteins M; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D054834:Lipocalins / Q000235:genetics*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D054834:Lipocalins; D004247:DNA; D008156:Luciferases