{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T13:53:42Z","timestamp":1726149222020},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T00:00:00Z","timestamp":1442880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Biotechnology, New Delhi, India","award":["BT\/PR13104\/MED\/12\/444\/2009"],"award-info":[{"award-number":["BT\/PR13104\/MED\/12\/444\/2009"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>This study aimed to evaluate the role of methylenetetrahydrofolate dehydrogenase (<jats:italic><jats:styled-content style=\"fixed-case\">MTHFD<\/jats:styled-content>1<\/jats:italic>) G1958A variant (rs2236225) as a \u2018maternal, paternal, or embryonic\u2019 genetic risk factor for neural tube defect (<jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>) susceptibility. It also estimated differential associations based on type of <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>, offspring sex, maternal\u2013paternal\u2013offspring genotype incompatibility, and parent\u2010of\u2010origin effects (<jats:styled-content style=\"fixed-case\">POE<\/jats:styled-content>) using both case\u2013control and family\u2010based approach. In addition, genotype impact on serum folate levels was also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>The study population (<jats:italic>n<\/jats:italic>=900) consisted of 120 <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content> case\u2010parent triads (<jats:italic>n<\/jats:italic>=120\u00d73=360) and 180 healthy control\u2010parent triads (<jats:italic>n<\/jats:italic>=180\u00d73=540) from South India. Umbilical cord tissues were collected from those with <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content> and control newborn infants, and blood samples from case and control parents. Genotyping was performed by polymerase chain reaction\u2013restriction fragment length polymorphism. Statistical analysis used were SPSS, transmission disequilibrium test and POE. Serum folate levels were estimated using enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the case\u2013control study, those with the <jats:italic><jats:styled-content style=\"fixed-case\">MTHFD<\/jats:styled-content>1<\/jats:italic> G1958A variant were associated with around twofold risk of anencephaly (<jats:italic>p<\/jats:italic>=0.01) and spina bifida (<jats:italic>p<\/jats:italic>&lt;0.01). Among parents, fathers were associated with around twofold risk of having an offspring with anencephaly (<jats:italic>p<\/jats:italic>&lt;0.01). Considering offspring sex, the A allele in single or double dose conferred around two\u2010 to fourfold risk of anencephaly (<jats:italic>p<\/jats:italic>=0.01), spina bifida (<jats:italic>p<\/jats:italic>&lt;0.01), and encephalocele (<jats:italic>p<\/jats:italic>&lt;0.05) in females only. Maternal <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content> genotype was not associated independently but conferred threefold risk when combined with paternal <jats:styled-content style=\"fixed-case\">GA<\/jats:styled-content> genotype (<jats:italic>p<\/jats:italic>=0.01). Transmission disequilibrium and <jats:styled-content style=\"fixed-case\">POE<\/jats:styled-content> were not observed in controls (<jats:italic>p<\/jats:italic>&gt;0.05) but revealed excess total (odds ratio [<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>]=2.21; <jats:italic>p<\/jats:italic>&lt;0.01) and paternal transmission (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>=7.00; <jats:italic>p<\/jats:italic>&lt;0.01) of the G1958A allele to those with spina bifida, which remained the same for female cases (total transmission <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>=3.00, <jats:italic>p<\/jats:italic>=0.01; paternal transmission <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>=12.00, <jats:italic>p<\/jats:italic>&lt;0.01). Increased serum folate levels were observed in case fathers with <jats:styled-content style=\"fixed-case\">GA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content> genotypes than control fathers (<jats:italic>p<\/jats:italic>&lt;0.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our research provides the first evidence supporting a paternal, rather than a maternal, transmission bias of <jats:italic><jats:styled-content style=\"fixed-case\">MTHFD<\/jats:styled-content>1<\/jats:italic> G1958A variant for <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content> susceptibility in the offspring.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dmcn.12929","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T05:29:39Z","timestamp":1442986179000},"page":"625-631","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Paternal transmission of <i><scp>MTHFD<\/scp>1<\/i> G1958A variant predisposes to neural tube defects in the offspring"],"prefix":"10.1111","volume":"58","author":[{"given":"Kattekola R","family":"Prasoona","sequence":"first","affiliation":[{"name":"Institute of Genetics and Hospital for Genetic Diseases Osmania University Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tella","family":"Sunitha","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Hospital for Genetic Diseases Osmania University Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Buragadda","family":"Srinadh","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Hospital for Genetic Diseases Osmania University Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madireddy L N","family":"Deepika","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Hospital for Genetic Diseases Osmania University Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiruvatturu M","family":"Kumari","sequence":"additional","affiliation":[{"name":"Modern Government Maternity Hospital Hyderabad Telangana India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akka","family":"Jyothy","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Hospital for Genetic Diseases Osmania University Hyderabad Telangana 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