TY - JOUR
T1 - Major genes regulating total serum immunoglobulin E levels in families with asthma
AU - Xu, Jianfeng
AU - Postma, Dirkje S.
AU - Howard, Timothy D.
AU - Koppelman, Gerard H.
AU - Zheng, Siqun L.
AU - Stine, O. Colin
AU - Bleecker, Eugene R.
AU - Meyers, Deborah A.
N1 - Funding Information:
We thank all of the families whose participation made this project possible. The research was supported in part by the Netherlands Asthma Foundation and by National Institutes of Health grant R01 HL48341. Some of the results reported in this article were obtained by use of the program package S.A.G.E., which is supported by U.S. Public Health Service Resource Grant 1 P41 RR03655 from the National Center for Research Resources.
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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U2 - 10.1086/321190
DO - 10.1086/321190
M3 - Article
C2 - 11023809
AN - SCOPUS:0033753931
VL - 67
SP - 1163
EP - 1173
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -