Major genes regulating total serum immunoglobulin E levels in families with asthma

Am J Hum Genet. 2000 Nov;67(5):1163-73. doi: 10.1086/321190. Epub 2000 Oct 6.


Immunoglobulin E (IgE) has a major role in the pathogenesis of allergic disorders and asthma. Previous data from 92 families, each identified through a proband with asthma, showed evidence for two major genes regulating total serum IgE levels. One of these genes mapped to 5q31-33. In the current study, the segregation analysis was extended by the addition of 108 probands and their families, ascertained in the same manner. A mixed recessive model (i.e., major recessive gene and residual genetic effect) was the best-fitting and most-parsimonious one-locus model of the segregation analysis. A mixed two-major-gene model (i.e., two major genes and residual genetic effect) fit the data significantly better than did the mixed recessive one-major-gene model. The second gene modified the effect of the first recessive gene. Individuals with the genotype aaBB (homozygous high-risk allele at the first gene and homozygous low-risk allele at the second locus) had normal IgE levels (mean 23 IU/ml), and only individuals with genotypes aaBb and aabb had high IgE levels (mean 282 IU/ml). A genomewide screening was performed using variance-component analysis. Significant evidence for linkage was found for a novel locus at 7q, with a multipoint LOD score of 3. 36 (P=.00004). A LOD score of 3.65 (P=.00002) was obtained after genotyping additional markers in this region. Evidence for linkage was also found for two previously reported regions, 5q and 12q, with LOD scores of 2.73 (P=.0002) and 2.46 (P=.0004), respectively. These results suggest that several major genes, plus residual genetic effects, regulate total serum IgE levels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asthma / genetics*
  • Asthma / immunology*
  • Asthma / pathology
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 7 / genetics
  • Female
  • Genes, Recessive / genetics
  • Genotype
  • Humans
  • Immunoglobulin E / blood*
  • Immunoglobulin E / immunology
  • Lod Score
  • Male
  • Middle Aged
  • Models, Genetic
  • Netherlands
  • Quantitative Trait, Heritable


  • Immunoglobulin E