| Project/Area Number |
16591111
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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 |
Dermatology
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| Research Institution | Nara Medical University |
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Principal Investigator |
MIYAGAWA Sachiko Nara Medical University, School of Medicine, Professor, 医学部, 教授 (30094626)
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| Co-Investigator(Kenkyū-buntansha) |
ASADA Hideo Nara Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (60252681)
NIIZEKI Hironori Nara Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (10228124)
INOKO Hidetoshi Tokai University, School of Medicine, Professor, 医学部・基礎医学系・分子生命科学, 教授 (10101932)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Pemphigus / Gene polymorphism / HLA / Desmoglein / Genome wide scan |
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| Research Abstract |
There is a consensus that HLA-DRB1 and -DQB1 are susceptible genes associated with the development of pemphigus. However, it is suggested that there might be numerous candidate genes in the disease. The purpose of this study is to discover novel single nucleotide polymorphisms (SNPs) to localize a susceptible locus within a particular candidate region. We studied desmoglein (DSG) cluster in chromosome 18q12 as a candidate region that encodes pemphigus-specific autoantigens.
To identify novel SNPs in the DSG1,DSG4, and DSG3 genes, we sequenced all exons including the flanking intronic sequence using direct sequencing. Genomic DNA extracted from peripheral blood was subjected from 8 patients with pemphigus vulgaris (PV) and 8 healthy controls.
We identified 14 SNPs in the DSG1 gene, 4 SNPs in the DSG4 gene, and 21 SNPs in the DSG3 gene. Several SNPs were identified in exon 1 and 16 (identical to exon 15 in the DSG1 gene) among all 3 genes. Exon 11 in the DSG1 and DSG3 gene includes a nonsynonymous SNP. Only one synonymous SNP in exon 7 in the DSG1 gene was found. This SNP was located in exon 2 to 10 to encode T cell epitopes in an extracellular domain of the desmoglein protein. It has been reported that this SNP (T809C) was associated with pemphigus foliaceus in the French and Tunisian populations. We identified the T809C SNP both in the patient and control group among Japanese in this study. Moreover, we also identified the PV-associated haplotype that includes 5 SNPs in the DSG3 gene reported by Capon, et al.
Haplotype association analysis using a large sample (N>160) we have already collected so far and functional analysis of these variants would enable us to provide evidence that the DSG genes are involved in the development of pemphigus through functional genetic polymorphisms.
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