Am. J. Respir. Crit. Care Med., Volume 158, Number 6, December 1998, 1825-1830

Linkage of Chromosome 5q and 11q Gene Markers to Asthma-associated Quantitative Traits in Australian Children

LYLE J. PALMER, SIW E. DANIELS, PETER J. RYE, NEIL A. GIBSON, GUAN K. TAY, WILLIAM O. C. M. COOKSON, JACK GOLDBLATT, PAUL R. BURTON, and PETER N. LESOUËF

Department of Paediatrics and Centre for Molecular Immunology and Instrumentation, University of Western Australia; Division of Biostatistics and Genetic Epidemiology, TVW Telethon Institute for Child Health Research, Perth, Australia; and Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom

Asthma is a genetically complex disease, and the investigation of putative linkages to candidate loci in independent populations is an important part of the gene discovery process. This study investigated the linkage of microsatellite markers in the 5q and 11q regions to asthma-associated quantitative traits in 121 Australian Caucasian nuclear families. The families were recruited on the basis of a child proband: a cohort of 95 randomly recruited families of unselected probands (n = 442 subjects) and a cohort of 26 families of probands selected on the basis of severe symptomatic asthma (n = 134 subjects). The quantitative traits assessed included serum levels of total IgE and specific IgE to house dust mite and mixed grass, blood eosinophil counts, and the dose-response slope (DRS) of FEV₁ to histamine provocation. Multipoint linkage analysis using Haseman-Elston sib-pair methods provided evidence of significant linkage between the chromosome 5q markers and log_e total serum IgE levels, specific serum IgE levels, and log_e blood eosinophil counts. The chromosome 11q markers showed evidence of significant linkage to specific serum IgE levels. Neither region demonstrated significant linkage to the log_e DRS to histamine. Phenotypes were residualized for age and sex. These data are consistent with the existence of loci regulating asthma-associated quantitative traits in both the 5q31-33 and 11q13 chromosomal regions.

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