1996 Fiscal Year Final Research Report Summary
Polymorphism in Drug Metabolism
| Project/Area Number |
07670489
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Seibo Jogakuin Women's College |
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Principal Investigator |
YAMADA Mitsuko Seibo Jogakuin Women's College, Department of Human Life Science, Associate Professor, 生活科学科, 助教授 (80145911)
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| Co-Investigator(Kenkyū-buntansha) |
NISHI Katsuji Shiga University of Medical Science, Department of Legal Medicine, Professor, 医学部, 教授 (60073681)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Drug Metabolism / Drug Pverdose / Drug Metabolizing Enzyme / Gene Diagnosis / Pharmacoanthropology / Forensic Toxickology |
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| Research Abstract |
Here we describe determination of genotypws of drug metabolizing enzymes and comparison of the nucleotide sequence among human and some mammals.
1) Samples examined
DNA samples were prepared from Japanese, German and some other populations and from three Japanese monkeys, a cat and three rabbits.
2) GSTM1 gene deletion
Glutathione S-transferase (GST) is a family of enzymes which catalyses the conjugation reaction with glutathione. GSTM1 is one of the genetic loci encoding human GST isoenzymes and is associated to the GSTu isoenzyme which is known to detoxify some compounds. We have examined the distribution of the GSTM1^<**>0/^<**>0 (gene deletion) genotype, which causes the GSTu isoenzyme deficiency. Almost 50% of people showed the gene deletion in the populations examined.
3) NAT2 genotype
N-Acetyltransferase (NAT) in human liver catalyzes N-acetylation of various arylamine-containing chemicals and N-Acetylation polymorphism is caused by polymorphic NAT (NAT2). We have determined the NAT1
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genotype. In Japanese sample 46% had ^<**>1/^<**>1 genotype and allele 4 was not found while 11% of Germans had ^<**>1/^<**>1 genotype and 73% had allele 4. It is known that the NATZ^<**>1 is considered to correspond to high N-acetylation activity and the ^<**>2, ^<**>3, ^<**>4, give rise to low. In the samples we have studied, 9% of Japanese and 54% of Germans were found to be slow-acetylator.
4) Partial sequence of the ALDH2 gene
Aldyhyde dehydrogenase (ALDH) is cound in various mammals. In human possessing the ALDH2^<**>2 allele a consequent elevation of blood acetaldehyde after ethanol intake due to less or no enzyme activity causes strong sensitivity to alcohol. We compared, to understand the evolutionary origin of the DNA polymorphism, the partial sequence of exon 12 in the human ALDH2 gene with that in mammals. In the animals we have studied the sequence showed considerable similarity to that of human. While in human the nucleotide at the 487th amino acid position, which is considered to be crucial in dividing humans into normal-and deficient-type, is adenine in ALDH2^<**>1 and guanine in ALDH2^<**>2, the nucleotide was found to be guanine in all the animals examined. Less
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