Major genes regulating total serum immunoglobulin E levels in families with asthma.
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.
Xu
J
J
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Postma
D S
DS
Howard
T D
TD
Koppelman
G H
GH
Zheng
S L
SL
Stine
O C
OC
Bleecker
E R
ER
Meyers
D A
DA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002648:Child; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009426:Netherlands; D019655:Quantitative Trait, Heritable
D007073:Immunoglobulin E