Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients, and maximum-likelihood estimation of combinatorial effect that two genetic loci have on susceptibility to the disease

Ryo Yamada, Toshihiro Tanaka, Motoko Unoki, Tatsuo Nagai, Tetsuji Sawada, Yozo Ohnishi, Tatsuhiko Tsunoda, Masao Yukioka, Akira Maeda, Kenji Suzuki, Hiroomi Tateishi, Takahiro Ochi, Yusuke Nakamura, Kazuhiko Yamamoto

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Genetic variants of interleukin-3 (IL-3), a well-studied cytokine, may have a role in the pathophysiology of rheumatoid arthritis (RA); but reports on this association sometimes conflict. A case-control study was designed to investigate association between RA and a single-nucleotide polymorphism (SNP) in the IL-3 promoter region. Comparison of cases of RA versus control individuals yielded a X2 value of 14.28 (P = .0002), with a genotype odds ratio of 2.24 (95% confidence interval [95%Cl] 1.44-3.49). When female cases with earlier onset were compared with female control individuals, the SNP revealed an even more significant correlation, with X2 = 21.75 (P = .000004) and a genotype odds ratio of 7.27 (95%CI 2.80-18.89). The stronger association that we observed in this clinically distinct subgroup (females with early onset), within a region where linkage disequilibrium was not significantly extended, suggested that the genuine RA locus should locate either within or close to the IL-3 gene. Combined genotype data on SNPs on eight other candidate genes were combined with our IL-3 results, to estimate relationships between pairs of loci and RA, by maximum-likelihood analysis. The utility of combining the genotype data in this way to identify possible contributions of various genes to this disease is discussed.

Original languageEnglish
Pages (from-to)674-685
Number of pages12
JournalAmerican journal of human genetics
Issue number3
Publication statusPublished - Jan 1 2001
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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