TY - JOUR
T1 - Major genes regulating total serum immunoglobulin E levels in families with asthma
AU - Xu, J.
AU - Postma, D. S.
AU - Howard, T. D.
AU - Koppelman, G. H.
AU - Zheng, S. L.
AU - Stine, O. C.
AU - Bleecker, E. R.
AU - Meyers, D. A.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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M3 - Article
C2 - 11023809
AN - SCOPUS:0033753931
SN - 0002-9297
VL - 67
SP - 1163
EP - 1173
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -