Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese

BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8 × 10(-10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)--POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)--and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma

ハクナイショウ モデル マウス RLC ニ オケル Dock180 ファミリー Dock5 ノ ヘンイ

京都大学0048新制・課程博士博士(医学)甲第14091号医博第3266号新制||医||970(附属図書館)UT51-2008-L147京都大学大学院医学研究科病理系専攻(主査)教授 武藤 誠, 教授 吉村 長久, 教授 藤田 潤学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Real-time polymerase chain reaction analysis of mRNA expression in anterior lens capsules

Total RNA was extracted from the anterior lens capsule of XFG/senile cataracts. Real-time PCR analysis was performed with expression assay probes. The amount of relative expression was normalized to that of 18Sr RNA. (N.S.: Not statistically significant, p=0.529; Mann–Whitney’s U-test).<p><b>Copyright information:</b></p><p>Taken from " genetic polymorphisms are associated with exfoliation glaucoma in the Japanese population"</p><p></p><p>Molecular Vision 2008;14():1037-1040.</p><p>Published online 05 Jun 2008</p><p>PMCID:PMC2426718.</p><p></p

Association results of genome-wide significant SNPs in the Present GWAS.

a<p>Risk allele frequency in POAG/controls.</p>b<p><i>P</i> value of combined 2 GWAS results by Mantel-Haenszel test.</p>c<p><i>P</i> value of Cochran's Q heterogeneity test between Previous and Present GWAS.</p

Study design.

<p>(A) We first performed the “Present GWAS” for POAG and identified the 9p21.3 locus. This result was confirmed by the combined analysis with the “Previous GWAS”. (B) We then subdivided the POAG subjects into two subtypes, POAG/HPG and POAG/NPG, and each group was analyzed by combining the two data sets in order to investigate the differences of statistical significance in the 9p21.3 locus.</p

Data_Sheet_1_Potential marker subset of blood-circulating cytokines on hematopoietic progenitor-to-Th1 pathway in COVID-19.pdf

In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of the proteins analyzed in COVID-19, approximately 70% were detected with Bonferroni-corrected significant differences in comparison with disease severity, clinical outcome, long-term hospitalization, and disease progression and recovery. Specifically, IP-10, sTNF-R1, sTNF-R2, sCD30, sCD163, HGF, SCYB16, IL-16, MIG, SDF-1, and fractalkine were found to be major components of the COVID-19 cytokine storm. Moreover, the 11 cytokines (i.e., SDF-1, SCYB16, sCD30, IL-11, IL-18, IL-8, IFN-γ, TNF-α, sTNF-R2, M-CSF, and I-309) were associated with the infection, mortality, disease progression and recovery, and long-term hospitalization. Increased expression of these cytokines could be explained in sequential pathways from hematopoietic progenitor cell differentiation to Th1-derived hyperinflammation in COVID-19, which might also develop a novel strategy for COVID-19 therapy with recombinant interleukins and anti-chemokine drugs.</p