Project/Area Number |
10670429
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
内科学一般
|
Research Institution | Teikyo University |
Principal Investigator |
KUWATA Shoji Dept. Internal medicine, Teikyo University Associate Professor, 医学部, 助教授 (00241993)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Hidemi Jichi Medical School, Dept. Dermatology, Professor, 医学部, 教授 (20114580)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
|
Keywords | melanoma / processing / peptide / transporter / TAP / HLA / HLA-DM / DNA / PCR |
Research Abstract |
We investigated polymorphisms of transporter associated with antigen processing (TAP) genes in patients with malignant melanoma. We developed polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP) method for discriminating TAP alleles. Genomic DNA was extracted from 37 Japanese patients with malignant melanoma and 52 control subjects with informed consent. Dimorphic regions of TAP1 and TAP2 genes were amplified by polymerase chain reaction (PCR). Amplified products were digested with restriction endonucleases to determine TAP alleles ; Sau3A1 for TAP1 codon 333 (Ile-Val), AccI for TAP1 codon 637 (Asp-Gly), and EcoRII for TAP2 codon 687 (Gln-Stop). We observed four alleles for TAP1 and dimorphism for TAP2 codon 687. Five out of 37 patients possessed TAP1 D allele which has been reported as a rare allele in Caucasian populations. Gene frequency of TAP1 637Asp exhibited a tendency of increase in the patients. TAP1 637Asp and TAP1 A allele were estimated to constitute a haplotype with DRB1ィイD1*ィエD11302-DQB1ィイD1*ィエD10604 and DRB1ィイD1*ィエD10803-DQB1ィイD1*ィエD10601 in Japanese population. As TAP1 and TAP2 genes are located between HLA-DQB1 and -DPB1 loci, analysis of TAP gene polymorphisms will be useful for better understanding of susceptibility loci in HLA associated disease. Further studies on deletion or mutation of beta 2 microglobulin will be needed for precise evaluation of melanoma antigen processing.
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