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

J. Xu, D. S. Postma, T. D. Howard, G. H. Koppelman, S. L. Zheng, O. C. Stine, E. R. Bleecker, D. A. Meyers

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1163-1173
Number of pages11
JournalAmerican Journal of Human Genetics
Volume67
Issue number5
StatePublished - 2000
Externally publishedYes

Fingerprint

Immunoglobulin E
Asthma
Serum
Genes
Recessive Genes
Alleles
Genotype
Analysis of Variance

ASJC Scopus subject areas

  • Genetics

Cite this

Xu, J., Postma, D. S., Howard, T. D., Koppelman, G. H., Zheng, S. L., Stine, O. C., ... Meyers, D. A. (2000). Major genes regulating total serum immunoglobulin E levels in families with asthma. American Journal of Human Genetics, 67(5), 1163-1173.

Major genes regulating total serum immunoglobulin E levels in families with asthma. / Xu, J.; Postma, D. S.; Howard, T. D.; Koppelman, G. H.; Zheng, S. L.; Stine, O. C.; Bleecker, E. R.; Meyers, D. A.

In: American Journal of Human Genetics, Vol. 67, No. 5, 2000, p. 1163-1173.

Research output: Contribution to journalArticle

Xu, J, Postma, DS, Howard, TD, Koppelman, GH, Zheng, SL, Stine, OC, Bleecker, ER & Meyers, DA 2000, 'Major genes regulating total serum immunoglobulin E levels in families with asthma', American Journal of Human Genetics, vol. 67, no. 5, pp. 1163-1173.
Xu J, Postma DS, Howard TD, Koppelman GH, Zheng SL, Stine OC et al. Major genes regulating total serum immunoglobulin E levels in families with asthma. American Journal of Human Genetics. 2000;67(5):1163-1173.
Xu, J. ; Postma, D. S. ; Howard, T. D. ; Koppelman, G. H. ; Zheng, S. L. ; Stine, O. C. ; Bleecker, E. R. ; Meyers, D. A. / Major genes regulating total serum immunoglobulin E levels in families with asthma. In: American Journal of Human Genetics. 2000 ; Vol. 67, No. 5. pp. 1163-1173.
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