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KMID : 0620920110430110613
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Experimental & Molecular Medicine
2011 Volume.43 No. 11 p.613 ~ p.621
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Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis
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Hu Hae-Jin
Jin Eun-Heui
Yim Seon-Hee
Yang So-Young
Jung Seung-Hyun
Shin Seung-Hun
Kim Wan-Uk
Shim Seung-Cheol
Kim Tai-Gyu
Chung Yeun-Jun
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Abstract
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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.
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KEYWORD
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APOM protein, human, autoimmune diseases, genome-wide association study, polymorphism, single nucleotide, rheumatoid arthritis
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