2011 Fiscal Year Final Research Report
Analyzing glaucoma-associated variants to reveal molecular mechanism of glaucoma pathogenesis
| Project/Area Number |
22790324
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
NAKANO Masakazu 京都府立医科大学, 医学研究科, 助教 (70381944)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 分子病態学 |
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| Research Abstract |
Glaucoma is a neurodegenerative ocular disease and one of the leading causes of irreversible blindness worldwide. It has been considered that genetic factors play a significant role in the pathogenesis of glaucoma, although only a small portion of the genetic variation for primary open-angle glaucoma(POAG), the major type of glaucoma, has been elucidated. We previously reported a genome-wide association study(GWAS), and identified six variants that were modestly associated with POAG(Nakano et al., PNAS, 106 : 12838-12842, 2009). However, the association result was not reproducible in the other studies. Therefore, in order to discover authentic variant(s) for POAG, we further performed a GWAS with an improved statistical power by analyzing 653, 519 autosomal common variants using a different Japanese population of 833 POAG patients and 686 controls. As a result, we successfully identified 5 variants that passed the Bonferroni correction in CDKN2B-AS1 on chromosome 9p21, a non-coding"gene desert"locus. We also subdivided the case group into two subtypes based on the measurement of intraocular pressure(IOP): POAG with high IOP(high pressure glaucoma, HPG) and that with normal IOP(normal pressure glaucoma, NPG), because most of the Japanese POAG patients(> 90%) were categorized into NPG group. Interestingly, we found that the variants from the same CDKN2B-AS1 locus were likely to be significant only for NPG patients. Since the variants of 9p21 found to be associated with a variety of common diseases and seemed to affect the expression of not only adjacent but also distant genes, it would be important to continue the detailed investigation by obtaining in-depth sequencing data across the locus in order to identify the target gene(s) and reveal the molecular mechanism of glaucoma pathogenesis.
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[Journal Article] Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese2012
Author(s)
Nakano, M., Ikeda, Y., Tokuda, Y., Fuwa, M., Omi, N., Ueno, M., Imai, K., Adachi, H., Kageyama, M., Mori, K., Kinoshita, S. and Tashiro, K
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Journal Title
PLoS ONE
Volume: 7
Pages: e33389
DOI
Peer Reviewed
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[Journal Article] Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level2010
Author(s)
Harismendy, O., Bansal, V., Bhatia, G., Nakano, M., Scott, M., Wang, X. C., Dib, C., Turlotte, E., Sipe, J. C., Murray, S. S., Deleuze, J. F., Bafna, V., Topol, E. J. and Frazer, K. A
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Journal Title
Genome Biol.
Volume: 11
Pages: R118
DOI
Peer Reviewed
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[Journal Article] Association between prostaglandin E receptor 3 polymorphisms and Stevens-Johnson syndrome identified by means of a genome-wide association study2010
Author(s)
Ueta, M., Sotozono, C., Nakano, M., Taniguchi, T., Yagi, T., Tokuda, Y., Fuwa, M., Inatomi, T., Yokoi, N., Tashiro, K. and Kinoshita, S
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Journal Title
J. Allergy Clin. Immunol.
Volume: 126
Pages: 1218-1225
DOI
Peer Reviewed
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[Presentation] 緑内障の主病型である原発開放隅角緑内障に関連する多型の網羅的解析2010
Author(s)
不破正博, 池田陽子, 中野正和, 谷口孝純, 徳田雄市, 大見奈津江, 八木知人, 田中雅深, 上野盛夫, 森和彦, 木下茂, 田代啓
Organizer
第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
Place of Presentation
神戸
Year and Date
2010-12-10
