| Project/Area Number |
10671628
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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 |
Otorhinolaryngology
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| Research Institution | The Kitasato Institute |
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Principal Investigator |
HASHIGUCHI Kazuhiro The Kitasato Institute, Chief of department, 北里研究所病院, 耳鼻咽喉科研究員 (80172849)
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| Co-Investigator(Kenkyū-buntansha) |
NIIZEKI Hironori National Tokyo Medical Center, Chief of department, 皮膚科研究員 (10228124)
SUZUKI Yukio The Kitasato Institute, Chief of department, 北里研究所病院, 内科研究員 (30196886)
YOKOYAMA Maki The Kitasato Institute, Chief of department, 北里研究所病院, 耳鼻咽喉科研究員 (80276360)
NISHIKAWA Takeji Keio University School of Medicine, Professor, 医学部, 教授 (50051579)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Palmoplantar pustulosis / Polymorphism / Tumor necrosis factor B gene / Tumor necrosis factor A promotor region / HLA-DR |
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| Research Abstract |
Palmoplantar pustulosis (PPP) is a chronic recurrent sterile pustulosis localized on the palms and soles. Although some immunological etiology has been suspected, its pathogenesis is still unknown. HLA typing of patients with PPP has shown that HLA-B8, -B14, and -Bw35 have been found to be increased in Caucasian, whereas only the HLA-DR9 antigen showed significant increase in frequency in Japanese patients. This difference may be explained not only by racial and ethnic differences among PPP patients but also by another susceptibility gene to the disease near or within the HLA region.
We investigated the alleleic and genotype distribution of a polymorphism of the tumor necrosis factor (TNF) B gene and the frequency of HLA-DR9 in 49 patients with palmoplantar pustulosis (PPP) and 51 healthy controls. We found that the frequency of TNFB2 was significantly increased in the PPP patients when compared with that in the controls. Furthermore, DR9-TNFB2 haplotype was significantly higher in freq
… More
uency in the PPP patients (p=0.0045), suggesting that the TNF region may confer susceptibility to PPP.
In order to detect the centromertic end of the susceptible locus in this disease, we conducted a further study to determine the TNFA gene polymorphisms in 80 patients with PPP. The 5'-flanking region of TNFA gene from -1107 to -66 was amplified by polymerase chain reaction. Nucleotide sequencing data revealed that 5 dinucleotide polymorphisms at -1031, -862, -856, -571, -307 and -237. None of the nucleotide substitution were significantly increased in PPP patients when compared with those in controls. To clarify the linkage among the neighboring genetic marker, we analyzed the association between the polymorphisms in the TNFA promoter region and the NcoI polymorphism in the first intron of TNFB gene as well as HLA-DR9. The genotype at -103C is strongly associated with TNFB1 and negatively associated with TNFB2 which is reported to be associated with PPP.
These data indicate that TNFA gene centrometric to TNFB is not associated with PPP and the susceptible gene of PPP is located between TNFB and HLA-B. Less
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