Am. J. Respir. Crit. Care Med., Volume 161, Number 3, March 2000, 700-706

Association Study of the Chromosomal Region Containing the FCER2 Gene Suggests It Has a Regulatory Role in Atopic Disorders

TARJA LAITINEN, VESA OLLIKAINEN, CONXI LÁZARO, PAULA KAUPPI, RAFAEL de CID, JOSEP MARIA ANTÓ, XAVIER ESTIVILL, HEIKKI LOKKI, HEIKKI MANNILA, LAURI A. LAITINEN, and JUHA KERE

Department of Medical Genetics, Haartman Institute, and Department of Computer Science, University of Helsinki, Helsinki; Division of Pulmonary Medicine and Clinical Physiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; Center for Medical and Molecular Genetics, Institut de Recerca Oncològica, Hospital Duran i Reynals, Barcelona; and Department of Epidemiology and Public Health, Institut Municipal d'Investigació Mèdica, Barcelona, Spain

On the basis of studies with animal models, the gene for the low-affinity receptor for immunoglobulin E (IgE) (FCER2, CD23) has been implicated as a candidate for IgE-mediated allergic diseases and bronchial hyperreactivity, or related traits. Given evidence for genetic complexity in atopic disorders, we sought to study two European subpopulations, Finnish and Catalonian. We studied three phenotypic markers: (1) total serum IgE level; (2) asthma; and (3) specific IgE level for a mixture of the most common aeroallergens in Finland. Altogether, eight polymorphic markers spanning a region of 10 cM around the FCER2 gene on chromosome 19p13 were analyzed in 124 families. The physical order of the markers and the location of the FCER2 gene were confirmed by using radiation hybrids. The allele and haplotype association study showed a suggestive haplotype association (signficance of p  0.03 based on a permutation test) for a high serum IgE response. In a subset of chromosomes segregating with asthma in families with two or more affected members, a single haplotype was found to be highly enriched (p = 8.3 × 10⁶). However, sequence polymorphisms, which would verify structural differences in the FCER2 gene, were not detected in the coding region of the receptor. Our results suggest that chromosome 19p13 might harbor a genetic determinant of IgE-related traits. Studies in other population samples are needed to verify this finding. Laitinen T, Ollikainen V, Lázaro C, Kauppi P, de Cid R, Antó JM, Estivill X, Lokki H, Mannila H, Laitinen LA, Kere J. Association study of the chromosomal region containing the FCER2 gene suggests it has a regulatory role in atopic disorders.

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