| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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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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