{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:21:56Z","timestamp":1756383716361},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008696","name":"University of the Punjab","doi-asserted-by":"crossref","award":["PU-19"],"award-info":[{"award-number":["PU-19"]}],"id":[{"id":"10.13039\/100008696","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Ventricular septal defects (VSDs) are malformations in the septum separating the heart\u2019s ventricles. VSDs may present as a single anomaly (<jats:italic>isolated\/nonsyndromic<\/jats:italic> VSD) or as part of a group of phenotypes (<jats:italic>syndromic<\/jats:italic> VSD). The exact location of the defect is crucial in linking the defect to the underlying genetic cause. The number of children visiting cardiac surgery units is constantly increasing. However, there are no representative data available on the genetics of VSDs in Pakistani children.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Two hundred forty-two subjects (121 VSD children and 121 healthy controls) were recruited from pediatric cardiac units of Lahore. The clinical and demographic data of the subjects were collected. A total of four SNPs, one each from <jats:italic>MTRR, GATA4<\/jats:italic>, <jats:italic>VEGF<\/jats:italic>, and <jats:italic>ISL1<\/jats:italic> genes were genotyped by PCR-RFLP.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The results showed that the minor allele (T) frequency (MAFs) for the <jats:italic>MTRR<\/jats:italic> gene variant rs1532268 (c.524C\u2009&gt;\u2009T) was 0.20 and 0.41 in the controls and the cases, respectively, with the genotype frequencies 3, 35, 62% in the controls and 12, 59 and 29% in the cases for TT, CT, CC genotypes, respectively (allelic OR: 5.73, CI: 3.82\u20138.61, <jats:italic>p-<\/jats:italic>value: 5.11\u2009\u00d7\u200910<jats:sup>\u2212\u20097<\/jats:sup>). For the <jats:italic>GATA4<\/jats:italic> variant rs104894073 (c.886G\u2009&gt;\u2009A), the MAF for the controls and the cases was 0.16 and 0.37, respectively, the frequencies of AA, GA and GG genotypes were 2, 28, and 70% in the controls and 5, 64 and 31% of the cases (allelic OR: 3.08, CI: 2.00\u20134.74, <jats:italic>p<\/jats:italic>-value: 8.36\u2009\u00d7\u200910<jats:sup>\u2212\u20098<\/jats:sup>). The rs699947 (c.-2578C\u2009&gt;\u2009A) of <jats:italic>VEGF<\/jats:italic> gene showed MAF 0.36 and 0.53 for the controls and cases, respectively, with the genotype frequencies 13, 42, and 45% in the controls and 22, 15, and 63% in the cases for the AA, CA, CC (allelic OR: 2.03, CI: 1.41\u20132.92, <jats:italic>p<\/jats:italic>-value: 0.0001). The <jats:italic>ISL1<\/jats:italic> gene variant rs6867206 (g.51356860\u2009T\u2009&gt;\u2009C), the MAFs were 0.26 and 0.31 in the controls and cases, respectively. The genotype frequencies were 48, 52, 0% in the controls and 39, 61, 0% in the cases for TT, TC, CC genotypes (allelic OR: 0.27, CI: 0.85\u20131.89, <jats:italic>p<\/jats:italic>-value: 0.227). The <jats:italic>MTRR<\/jats:italic>, <jats:italic>GATA4<\/jats:italic> and <jats:italic>VEGF<\/jats:italic> variants showed association while <jats:italic>ISL1<\/jats:italic> variant did not appear to be associated with the VSD in the recruited cohort.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This first report in Pakistani children demonstrates that single nucleotide polymorphisms in genes encoding transcription factors, signaling molecules and structural heart genes involved in fetal heart development are associated with developmental heart defects., however further work is needed to validate the results of the current investigation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13052-021-01022-7","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T18:03:58Z","timestamp":1616522638000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["First report of polymorphisms in MTRR, GATA4, VEGF, and ISL1 genes in Pakistani children with isolated ventricular septal defects (VSD)"],"prefix":"10.1186","volume":"47","author":[{"given":"Sumbal","family":"Sarwar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farah","family":"Ehsan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Shabana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amna","family":"Tahir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahrukh","family":"Jamil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saleem Ullah","family":"Shahid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asim","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahida","family":"Hasnain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"1022_CR1","doi-asserted-by":"crossref","unstructured":"Setty HSSN, Patil SSG, Ramegowda RT, Vijayalakshmi IB, Manjunath CN. 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A written informed consent was obtained from all recruited subjects or parent\/guardian (for children under 15\u2009years of age).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"There is no conflict of interests regarding the publication of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}