{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:30:00Z","timestamp":1782819000352,"version":"3.54.5"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,9,20]]},"abstract":"\n Background<\/jats:title>\n \n There are conflicting reports with regard to the allele\u2010specific gene suppression effects of single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of the\n KCNQ1<\/jats:italic>\n gene in long QT syndrome type 1 (LQT1) populations. Here we assess the allele\u2010specific effects of 3 previously published 3'UTR\u2010\n KCNQ1<\/jats:italic>\n 's SNPs in a LQT1 founder population segregating a dominant\u2010negative mutation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Bidirectional sequencing of the\n KCNQ1<\/jats:italic>\n '\n s<\/jats:italic>\n 3'UTR was performed in the p.Y111C founder population (n=232, 147 genotype positive), with a minor allele frequency of 0.1 for SNP1 (rs2519184) and 0.6 for linked SNP2 (rs8234) and SNP3 (rs107980). Allelic phase was assessed in trios aided by haplotype data, revealing a high prevalence of derived SNP2\/3\n in cis<\/jats:italic>\n with p.Y111C (89%). Allele\u2010specific association analyses, corrected using a relatedness matrix, were performed between 3'UTR\u2010\n KCNQ1<\/jats:italic>\n SNP genotypes and clinical phenotypes. SNP1\n in trans<\/jats:italic>\n was associated with a significantly higher proportion of symptomatic phenotype compared with no derived SNP1 allele\n in trans<\/jats:italic>\n (58% versus 32%, corrected\n P<\/jats:italic>\n =0.027). SNP2\/3\n in cis<\/jats:italic>\n was associated with a significantly lower proportion of symptomatic phenotype compared with no derived SNP2\/3 allele\n in cis<\/jats:italic>\n (32% versus 69%, corrected\n P<\/jats:italic>\n =0.010).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Allele\u2010specific modifying effects on symptomatic phenotype of 3'UTR\u2010\n KCNQ1<\/jats:italic>\n SNPs rs2519184, rs8234, and rs107980 were seen in a LQT1 founder population segregating a dominant\u2010negative mutation. The high prevalence of suppressive 3'UTR\u2010\n KCNQ1<\/jats:italic>\n SNPs segregating with the founder mutation could contribute to the previously documented low incidence of cardiac events in heterozygous carriers of the p.Y111C\n KCNQ1<\/jats:italic>\n mutation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.122.025981","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T09:37:33Z","timestamp":1663148253000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["To Modify or Not to Modify: Allele\u2010Specific Effects of 3'UTR\u2010\n KCNQ1<\/i>\n Single Nucleotide Polymorphisms on Clinical Phenotype in a Long QT 1 Founder Population Segregating a Dominant\u2010Negative Mutation"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-3166","authenticated-orcid":false,"given":"Annika","family":"Winbo","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Pediatrics Ume\u00e5 University Ume\u00e5 Sweden"},{"name":"Department of Physiology University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1811-225X","authenticated-orcid":false,"given":"Ulla\u2010Britt","family":"Diamant","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine Heart Centre, Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7766-8557","authenticated-orcid":false,"given":"Johan","family":"Persson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Pediatrics Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5275-2544","authenticated-orcid":false,"given":"Steen M.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Public Health and Clinical Medicine Heart Centre, Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-7783","authenticated-orcid":false,"given":"Annika","family":"Rydberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Pediatrics Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/302938"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2010.12.035"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2018.09.007"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr473"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001419"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001629"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001635"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2010.11.043"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.108.825547"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00031.2005"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000250262.12219.95"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-017-0435-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2006.00408.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/378208"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20418"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2013.10.005"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.572453"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.726950"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.025981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:08:28Z","timestamp":1715598508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.025981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":18,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2022,9,20]]}},"alternative-id":["10.1161\/JAHA.122.025981"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.025981","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,20]]},"assertion":[{"value":"2022-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e025981"}}