{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T09:48:19Z","timestamp":1782035299411,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T00:00:00Z","timestamp":1606521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A5A2021242"],"award-info":[{"award-number":["2018R1A5A2021242"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phosphodiesterase 3A (PDE3A) is an enzyme that plays an important role in the regulation of cyclic adenosine monophosphate (cAMP)\u2013mediated intracellular signaling in cardiac myocytes and platelets. PDE3A hydrolyzes cAMP, which results in a decrease in intracellular cAMP levels and leads to platelet activation. Whole\u2010exome sequencing of 50 DNA samples from a healthy Korean population revealed a total of 13 single nucleotide polymorphisms including five missense variants, D12N, Y497C, H504Q, C707R, and A980V. Recombinant proteins for the five variants of PDE3A (and wild\u2010type protein) were expressed in a FreeStyle 293 expression system with site\u2010directed mutagenesis. The expression of the recombinant PDE3A proteins was confirmed with Western blotting. Catalytic activity of the PDE3A missense variants and wild\u2010type enzyme was measured with a PDE\u2010based assay. Effects of the missense variants on the inhibition of PDE3A activity by cilostazol were also investigated. All variant proteins showed reduced activity (33\u201353%; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.0001) compared to the wild\u2010type protein. In addition, PDE3A activity was inhibited by cilostazol in a dose\u2010dependent manner and was further suppressed in the missense variants. Specifically, the PDE3A Y497C showed significantly reduced activity, consistent with the predictions of in silico analyses. The present study provides evidence that individuals carrying the PDE3A Y497C variant may have lower enzyme activity for cAMP hydrolysis, which could cause interindividual variation in cAMP\u2010mediated physiological functions.<\/jats:p>","DOI":"10.1111\/ahg.12411","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T07:54:21Z","timestamp":1606636461000},"page":"80-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (<i>PDE3A<\/i>)"],"prefix":"10.1111","volume":"85","author":[{"given":"You Ran","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacogenomics Research Center Inje University College of Medicine Inje University  Busan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MyeongJin","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacogenomics Research Center Inje University College of Medicine Inje University  Busan South Korea"},{"name":"Pharmacogenetics Section, Reproductive and Developmental Biology Laboratory National Institute of Environmental Health Sciences National Institutes of Health  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun\u2010Ah","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacogenomics Research Center Inje University College of Medicine Inje University  Busan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacogenomics Research Center Inje University College of Medicine Inje University  Busan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JungKi","family":"Min","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory National Institute of Environmental Health Sciences, NIH  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Gook","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacogenomics Research Center Inje University College of Medicine Inje University  Busan South Korea"},{"name":"Department of Clinical Pharmacology Inje University Busan Paik Hospital Inje University College of Medicine Inje University  Busan 47392 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacogenomics Research Center Inje University College of Medicine Inje University  Busan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12275"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.638585"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2013-1053"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.213348"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-S2-S6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1998.0915"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2018.04.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3530041"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1416230112"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2011.09.015"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.043061"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002907"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00641.2013"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3316"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606558200"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807536200"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3405"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00487-10"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2019.103781"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.6"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3302"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd5010010"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.58.2.247"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)43866-5"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117825"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-29423-5_9"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000087541.15600.2B"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.12.053"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni103"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-009-9135-0"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2020.02.027"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.13513"},{"issue":"4","key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.kint.2016.03.037","article-title":"The case| A handful of hypertension","volume":"90","author":"den Born B. J.","year":"2016","journal-title":"Kidney International"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203647200"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2017.03.010"},{"issue":"2","key":"e_1_2_9_39_1","first-page":"109","article-title":"Intravenous milrinone in treatment of advanced congestive heart failure","volume":"30","author":"Zewail A. M.","year":"2003","journal-title":"Texas Heart Institute Journal"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.6601"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12411","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.12411","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12411","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T03:29:04Z","timestamp":1693538944000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.12411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,28]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/ahg.12411"],"URL":"https:\/\/doi.org\/10.1111\/ahg.12411","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,28]]},"assertion":[{"value":"2020-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}