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

Abstract

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 chi(2) value of 14.28 (P=.0002), with a genotype odds ratio of 2.24 (95% confidence interval [95%CI] 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 chi2=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.

Interleukin 3 and schizophrenia: the impact of sex and family history

“…69,70 Clinical studies show that IL3 activity may be lower in schizophrenia patients. 17,71 The nonsynonymous marker, rs40401, is reported to be associated with rheumatoid arthritis 72 that is negatively correlated with schizophrenia. 73 In summary, we present evidence that variants in and around IL3 are associated with schizophrenia in the ISHDSF, ICCSS and ITRIO samples.…”

A single-nucleotide substitution from C to T at position −1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand

“…An SNP at À16 in the promoter of IL-3 (IL-3 À16T4C) has been reported to be strongly associated with rheumatoid arthritis, although functional significance of this SNP remains unclear. 8 An SNP located at À590 upstream of the open reading frame of IL-4 (IL-4 À590C4T) has been reported to influence the promoter activity and to be associated with the total serum IgE. 9 More recently, this polymorphism was found to be associated with elevated antibody levels against malaria antigens in the Fulani of West Africa.…”

High-resolution SNP map of ASPN, a susceptibility gene for osteoarthritis

“…Since the genotype of each individual cannot be obtained by this method, we subsequently performed genotyping of individual samples using another 96 Japanese samples. Calculation of Hardy-Weinberg equilibrium linkage disequilibrium (LD) coefficient (D¢) was as described (Yamada et al 2001). Haplotype frequencies were estimated using SNPAlyze software (DYNACOM, Chiba, Japan).…”