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Molecular Medicine

, Volume 13, Issue 9–10, pp 455–460 | Cite as

Association of STAT4 with Rheumatoid Arthritis in the Korean Population

  • Hye-Soon Lee
  • Elaine F. Remmers
  • Julie M. Le
  • Daniel L. Kastner
  • Sang-Cheol Bae
  • Peter K. Gregersen
Research Article

Abstract

A recent study in the North American White population has documented the association of a common STAT4 haplotype (tagged by rs7574865) with risk for rheumatoid arthritis (RA) and systemic lupus erythematosus. To replicate this finding in the Korean population, we performed a case-control association study. We genotyped 67 single nucleotide polymorphisms (SNPs) within the STAT1 and STAT4 regions in 1123 Korean patients with RA and 1008 ethnicity-matched controls. The most significant four risk SNPs (rs11889341, rs7574865, rs8179673, and rs10181656 located within the third intron of STAT4) among 67 SNPs are identical with those in the North American study. All four SNPs have modest risk for RA susceptibility (odds ratio 1.21–1.27). A common haplotype defined by these markers (TTCG) carries significant risk for RA in Koreans [34 percent versus 28 percent, P = 0.0027, OR (95 percent CI) = 1.33 (1.10–1.60)]. By logistic regression analysis, this haplotype is an independent risk factor in addition to the classical shared epitope alleles at the HLA-DRB1 locus. There were no significant associations with age of disease onset, radiographic progression, or serologic status using either allelic or haplotypic analysis. Unlike several other risk genes for RA such as PTPN22, PADI4, and FCRL3, a haplotype of the STAT4 gene shows consistent association with RA susceptibility across Whites and Asians, suggesting that this risk haplotype predates the divergence of the major racial groups.

Notes

Acknowledgments

This work was made possible by support from the Eileen Ludwig Greenland Center for Rheumatoid Arthritis. Additional support was provided by grants from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ3-PG6-01GN11-0002), the National Institutes of Health, RO1-AR44222 (PKG) and the intramural program of the National Institutes of Arthritis and Musculoskeletal and Skin Diseases.

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Copyright information

© Feinstein Institute for Medical Research 2007

Authors and Affiliations

  • Hye-Soon Lee
    • 1
    • 2
  • Elaine F. Remmers
    • 3
  • Julie M. Le
    • 3
  • Daniel L. Kastner
    • 3
  • Sang-Cheol Bae
    • 2
  • Peter K. Gregersen
    • 1
  1. 1.Robert S Boas Center for Genomics and Human GeneticsFeinstein Institute for Medical Research, North Shore LIJ Health SystemManhassetUSA
  2. 2.The Hospital for Rheumatic DiseasesHanyang University Medical CenterSeoulSouth Korea
  3. 3.The National Institute of Arthritis and Musculoskeletal and Skin DiseasesBethesdaUSA

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