1. ¹Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan
2. ²Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan

Correspondence: Dr E Noguchi, Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki-ken 305-8575, Japan. E-mail: enoguchi@md.tsukuba.ac.jp

Received 5 March 2002; Revised 30 April 2002; Accepted 4 July 2002.

Abstract

Hepatitis A virus receptor (HAVcr-1) and T-cell immunoglobulin- and mucin-domain-containing molecule (TIM)-3 were recently implicated as asthma susceptibility genes in the study of congenic mice. In a genome-wide screen, we found strong evidence for linkage of atopic asthma with marker D5S820, located approximately 0.5 Mb from hHAVcr-1 and human TIM3. We screened for mutations in human HAVcr-1 (hHAVcr-1) and in TIM3 and found seven, including two insertion/deletion polymorphisms, in hHAVcr-1 and two in TIM3. We conducted transmission disequilibrium tests (TDTs) in families identified through children with atopic asthma. None of the hHAVcr-1 allele were transmitted preferentially to asthma-affected children (P>0.1). In quantitative TDT analysis, no association was observed between the log[total IgE] and either allele of the hHAVcr-1 polymorphism (P>0.1). The two TIM3 mutations were rare in the Japanese population, occurring in only one of 48 unrelated asthmatic subjects. Our results indicate that hHAVcr-1 polymorphisms are not likely to be associated with the development of atopy-related phenotypes in the Japanese population.