|Budget Amount *help
¥7,700,000 (Direct Cost : ¥7,700,000)
Fiscal Year 1998 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1997 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1996 : ¥6,100,000 (Direct Cost : ¥6,100,000)
1. Polymorphism of HMT gene
To date, according to our previous report and the report by R Weishilboum, two changes of nucleotide sequence in coding region. Nucleotide 314 within codon 105 is a T or a C, resulting in codons that encode isoleucine or threonine. Nucleotide 595 within codon 199 is an A or a G, resulting isoleucine or vatine. In addition, we found clones which lack of 8 nuleotides (CTAACAAA) in ncleotide 89 of first exon. Furthermore CA repeat sequence near 6th exon was polymorphic and we analysed the niumber of CA repeat among 100 normal individuals. As a result, CA repeat number distributed from 15 to 30 and was thought to be a useful marker of polymorphism of MHT gene.
2. Genetic linckage of HMT gene to bronchial asthma
The airway hyperresponsiveness, a critical factor of bronchial asthma, has been recognized as one of physical characteristics inherited genetically. The level of HMT activity is closely associated with airway contractile response to histamine in guinea pigs
(Nakazawa et al. , Am.J.Respir. Crit. Care Med. 1994, Hoshi et al. Am. J.Respir.Cell Mol. Biol. 1996). In this regard, to examine whether I-lIMIT gene is linked to bronchial asthma, we compared polymorphism of asthmatics to that of normal individuals. Aa a result, the distribution of CA repeat number was significantly different from that of normal individuals. Especially, CA repeat size smaller than 20 seemed to be a risk factor for bronchial asthma. Concerning the polymorphism influencing enzyme activity, HMT activity in the tissue of the individuals with 314T/C and 314T/T is lowerthan that with 314C/C.In this regard, we determined the pattern of 314 bases among 100 normal individuals and 100 asthmatics. As a result, because of small population of individuals with 314T/C (less than 10%), there was no significant difference between normals and asthma. To perform further analysis, we need to analyze the data on larger population of both normals and asthmatics.