TY - JOUR
T1 - 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
AU - Yamada, Ryo
AU - Tanaka, Toshihiro
AU - Unoki, Motoko
AU - Nagai, Tatsuo
AU - Sawada, Tetsuji
AU - Ohnishi, Yozo
AU - Tsunoda, Tatsuhiko
AU - Yukioka, Masao
AU - Maeda, Akira
AU - Suzuki, Kenji
AU - Tateishi, Hiroomi
AU - Ochi, Takahiro
AU - Nakamura, Yusuke
AU - Yamamoto, Kazuhiko
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1086/318789
DO - 10.1086/318789
M3 - Article
C2 - 11179015
AN - SCOPUS:0035094852
VL - 68
SP - 674
EP - 685
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -