ASSOCIATION BETWEEN HIGH SERUM TOTAL IGE LEVELS AND D11S97 ON CHROMOSOME 11Q13 IN JAPANESE SUBJECTS

The genetic linkage of atopy to chromosome 11q13 through maternally de rived alleles has been previously reported. Linkage analysis in Japane se families did not confirm the existence of a major gene for atopy at this locus under the model of autosomal dominant inheritance. However , we observed a significant association between serum total IgE levels and genetic markers at this locus both in 14 Japanese atopic families and in 120 unrelated Japanese subjects. We detected eight alleles at the D11S97 locus and eight alleles in the CA/GT repeat region in the f ifth intron of the Fc epsilon RI beta gene. A significantly increased frequency of the D11S97/PstI 0.96 kb allele was observed in the chromo somes of the subjects with high serum total IgE levels both in the fam ily study (p<0.001) and in the population study (p<0.05). However, mul tipoint linkage analysis again did not show any evidence for the exist ence of a major gene regulating atopy on chromosome 11q13 with locatio n scores to -35 under the model of maternal inheritance. Evidence agai nst linkage was confirmed by the non-parametric linkage analysis, usin g the affected pedigree member method. Also, there was no substitution of isoleucine for leucine in the fourth transmembrane domain of Fc ep silon RI beta (Leu181), which was reported to be responsible for a sub set of atopy in the British population. Therefore, the association of serum total IgE levels with chromosome 11q13 indicates that a gene or genes at this locus may contribute to the expression of high IgE level s in the Japanese population as well as in the British population, but the heterogeneity of the genetic regulation of serum total IgE levels is evident between the two populations.