J Asthma Allergy Clin Immunol.  1998 Dec;18(4):689-700.

Linkage analysis between gene marker of chromosome 11q13, and skin reactivity to common inhalant allergens and bronchial responsiveness in sib-pairs with probands of asthmatic children

• Kim YK
• Son JW
• Cho SH
• Lee MH
• Koh YY
• Min KU
• Kim YY

Abstract

BACKGROUND: Increased IgE antibody responses to inhalant allergens and bronchial hyperresponsiveness are important phenotypes in development of asthma. Although heredity reported to be important in expression of these phenotypes in twin and family studies, genetic factor(s) controlling these phenotypes is unknown.
OBJECTIVE
To evaluate whether genetic factor in chromosome 11q13 may control the expression of IgE responses to common inhalant allergens and bronchial hyperresponsiveness, linkage analysis between these phenotypes and gene marker of chromosome 11q13 was investigated.
MATERIALS AND METHODS
The phenotyping and genotyping using microsatellite marker (D11S97) were performed in 77 probands with bronchial asthma and 80 their sibs. The linkage analysis between these phenotypes and the genotype was evaluated by affected or quantitative trait locus (QTL) sib-pair analysis.
RESULTS
Positive skin test responses to inhalant allergens were 55/77(71.4%) in probands and 44/79(55.6%) in sibs, respectively. Positive bronchial provocation test responses to methacholine were 27/61(44.3%) in sibs, geometric mean of PC20-methacholine were 5.2 mg/ ml in probands and 39.4 mg/ml in sibs, respectively, and slope of dose response curve(mean+- SE, %/mg/ml) were 11.3 +- 3.22 in probands and 1.97 +- 0.5 in sibs, respectively. Of 34 sib-pairs with positive skin test responses to allergens, two D11S97 alleles were shared by 21(61.8% ) sib -pairs, one allele by 11(32.3% ) sib-pairs, and no identical allele by two(5.9% ) sib-pairs. In affected sib-pairs, sharing rate of the alleles was 77.9%, which indicates linkage of the phenotype and genotype(p<0.001). Of 25 sib-pairs with bronchial hyperresponsiveness to methacholine, two D11S97 alleles were shared by seven(28%) sib-pairs, one allele by 11(44%) sib-pairs, and no identical allele by seven(28% ) sib-pairs. In affected sib-pairs, sharing rate of the alleles was 50%, which indicates no linkage between the phenotype and genotype(p) 0.05). Differences of geometric value(mean +- SE) of PC-methacholine and slope of dose response curve(mean +- SE, %/mg/ml) were 1.11+- 0.17 and 8.33+- 3.35 in sib-pairs sharing two alleles, respectively, 0.99 +- 0.14 and 14.27+-5.75 in sib-pairs sharing one allele, respectively, and 0.57+-0.13 and 3.64+-1.62 in sib-pairs sharing no allele, respectively. There was no difference of the above values among the three groups.
CONCLUSION
The expression of skin reactivity to common inhalant allergens was linked to gene marker of chromosome 11q13, not with bronchial responsiveness to methacholine.

Keyword

bronchial asthma; skin reactivity; chromosome 11q13; sib-pair analysis

MeSH Terms

Alleles
Allergens*
Antibody Formation
Asthma
Bronchial Provocation Tests
Child*
Genotype
Heredity
Humans
Immunoglobulin E
Methacholine Chloride
Microsatellite Repeats
Phenotype
Quantitative Trait Loci
Skin Tests
Skin*
Allergens
Immunoglobulin E
Methacholine Chloride