{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:45:57Z","timestamp":1781779557322,"version":"3.54.5"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Myopia is the most common cause of refractive error worldwide. High myopia is a severe type of myopia, which usually accompanies pathological changes in the fundus. To identify high myopia susceptibility genes, DNA-pooling based genome-wide association analysis was used to search for a correlation between single nucleotide polymorphisms and high myopia in a Han Chinese cohort (cases vs. controls in discovery stage: 507 vs. 294; replication stage 1: 991 vs. 1,025; replication stage 2: 1,021 vs. 52,708). Three variants (rs10889602T\/G, rs2193015T\/C, rs9676191A\/C) were identified as being significantly associated with high myopia in the discovery, and replication stage. rs10889602T\/G is located at the third intron of phosphodiesterase 4B (<jats:italic>PDE4B<\/jats:italic>), whose functional assays were performed by comparing the effects of rs10889602T\/T deletion of this risk allele on <jats:italic>PDE4B<\/jats:italic> and <jats:italic>COL1A1<\/jats:italic> gene and protein expression levels in the rs10889602T\/T<jats:sup>del\/del<\/jats:sup>, rs10889602T\/T<jats:sup>del\/wt<\/jats:sup>, and normal control A549 cell lines. The declines in the <jats:italic>PDE4B<\/jats:italic> and <jats:italic>COL1A1<\/jats:italic> gene expression levels were larger in the rs10889602T\/T deleted A549 cells than in the normal control A549 cells (one-way ANOVA, <jats:italic>p<\/jats:italic> &amp;lt; 0.001). The knockdown of <jats:italic>PDE4B<\/jats:italic> by siRNA in human scleral fibroblasts led to downregulation of COL1A1. This correspondence between the declines in rs10889602 of the <jats:italic>PDE4B<\/jats:italic> gene, <jats:italic>PDE4B<\/jats:italic> knockdown, and COL1A1 protein expression levels suggest that <jats:italic>PDE4B<\/jats:italic> may be a novel high myopia susceptibility gene, which regulates myopia progression through controlling scleral collagen I expression levels. More studies are needed to determine if there is a correlation between <jats:italic>PDE4B<\/jats:italic> and high myopia in other larger sample sized cohorts.<\/jats:p>","DOI":"10.3389\/fgene.2021.775797","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T07:02:40Z","timestamp":1641970960000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["PDE4B Proposed as a High Myopia Susceptibility Gene in Chinese Population"],"prefix":"10.3389","volume":"12","author":[{"given":"Fuxin","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Reinach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suh-Hang H.","family":"Juo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenglin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anquan","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Ling","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqing","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangtian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: Analysis and Visualization of LD and Haplotype Maps","volume":"21","author":"Barrett","year":"2005","journal-title":"Bioinformatics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00439-009-0626-9","article-title":"Identification of Susceptibility Genes for Complex Diseases Using Pooling-Based Genome-wide Association Scans","volume":"125","author":"Boss\u00e9","year":"2009","journal-title":"Hum. 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