BACKGROUND: Arsenic induces neural tube defects in many animal models. Additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced neural tube defects. We sought to determine whether 14 single-nucleotide polymorphisms in genes involved in folate metabolism modified the effect of exposure to drinking water contaminated with inorganic arsenic and posterior neural tube defect (myelomeningocele) risk. METHODS: Fifty-four mothers of children with myelomeningocele and 55 controls were enrolled through clinical sites in rural Bangladesh in a case-control study of the association between environmental arsenic exposure and risk of myelomeningocele. We assessed participants for level of myelomeningocele, administered questionnaires, conducted biological and environmental sample collection, and performed genotyping. Inductively coupled plasma mass spectrometry was used to measure inorganic arsenic concentration in drinking water. Candidate single-nucleotide polymorphisms were identified through review of the literature. RESULTS: Drinking water inorganic arsenic concentration was associated with increased risk of myelomeningocele for participants with 4 of the 14 studied single-nucleotide polymorphisms in genes involved in folate metabolism: the AA/AG genotype of rs2236225 (MTHFD1), the GG genotype of rs1051266 (SLC19A1), the TT genotype of rs7560488 (DNMT3A), and the GG genotype of rs3740393 (AS3MT) with adjusted odds ratio of 1.13, 1.31, 1.20, and 1.25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively. CONCLUSION: Our results support the hypothesis that environmental arsenic exposure increases the risk of myelomeningocele by means of interaction with folate metabolic pathways.
BACKGROUND:Arsenic induces neural tube defects in many animal models. Additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced neural tube defects. We sought to determine whether 14 single-nucleotide polymorphisms in genes involved in folate metabolism modified the effect of exposure to drinking water contaminated with inorganic arsenic and posterior neural tube defect (myelomeningocele) risk. METHODS: Fifty-four mothers of children with myelomeningocele and 55 controls were enrolled through clinical sites in rural Bangladesh in a case-control study of the association between environmental arsenic exposure and risk of myelomeningocele. We assessed participants for level of myelomeningocele, administered questionnaires, conducted biological and environmental sample collection, and performed genotyping. Inductively coupled plasma mass spectrometry was used to measure inorganic arsenic concentration in drinking water. Candidate single-nucleotide polymorphisms were identified through review of the literature. RESULTS:Drinking waterinorganic arsenic concentration was associated with increased risk of myelomeningocele for participants with 4 of the 14 studied single-nucleotide polymorphisms in genes involved in folate metabolism: the AA/AG genotype of rs2236225 (MTHFD1), the GG genotype of rs1051266 (SLC19A1), the TT genotype of rs7560488 (DNMT3A), and the GG genotype of rs3740393 (AS3MT) with adjusted odds ratio of 1.13, 1.31, 1.20, and 1.25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively. CONCLUSION: Our results support the hypothesis that environmental arsenic exposure increases the risk of myelomeningocele by means of interaction with folate metabolic pathways.
Authors: Analee J Etheredge; Richard H Finnell; Suzan L Carmichael; Edward J Lammer; Huiping Zhu; Laura E Mitchell; Gary M Shaw Journal: Am J Med Genet A Date: 2012-08-17 Impact factor: 2.802
Authors: Maria Tellez-Plaza; Matthew O Gribble; V Saroja Voruganti; Kevin A Francesconi; Walter Goessler; Jason G Umans; Ellen K Silbergeld; Eliseo Guallar; Nora Franceschini; Kari E North; Wen H Kao; Jean W MacCluer; Shelley A Cole; Ana Navas-Acien Journal: Environ Health Perspect Date: 2013-01-15 Impact factor: 9.031
Authors: Faith Pangilinan; Anne M Molloy; James L Mills; James F Troendle; Anne Parle-McDermott; Caroline Signore; Valerie B O'Leary; Peter Chines; Jessica M Seay; Kerry Geiler-Samerotte; Adam Mitchell; Julia E VanderMeer; Kristine M Krebs; Angelica Sanchez; Joshua Cornman-Homonoff; Nicole Stone; Mary Conley; Peadar N Kirke; Barry Shane; John M Scott; Lawrence C Brody Journal: BMC Med Genet Date: 2012-08-02 Impact factor: 2.103
Authors: John F Obrycki; Jane J Lee; Kush Kapur; Ligi Paul; Md Omar Sharif Ibne Hasan; Selim Mia; Quazi Quamruzzaman; David C Christiani; Maitreyi Mazumdar Journal: Birth Defects Res Date: 2019-04-15 Impact factor: 2.344
Authors: Jannah Tauheed; Marco Sanchez-Guerra; Jane J Lee; Ligi Paul; Md Omar Sharif Ibne Hasan; Quazi Quamruzzaman; Jacob Selhub; Robert O Wright; David C Christiani; Brent A Coull; Andrea A Baccarelli; Maitreyi Mazumdar Journal: Epigenetics Date: 2017-04-07 Impact factor: 4.528
Authors: Jonathan Suhl; Stephanie Leonard; Peter Weyer; Anthony Rhoads; Anna Maria Siega-Riz; T Renée Anthony; Trudy L Burns; Kristin M Conway; Peter H Langlois; Paul A Romitti Journal: Birth Defects Res Date: 2018-10-27 Impact factor: 2.344
Authors: Megan M Niedzwiecki; Xinhua Liu; Huiping Zhu; Megan N Hall; Vesna Slavkovich; Vesna Ilievski; Diane Levy; Abu B Siddique; Muhammad G Kibriya; Faruque Parvez; Tariqul Islam; Alauddin Ahmed; Ana Navas-Acien; Joseph H Graziano; Richard H Finnell; Habibul Ahsan; Mary V Gamble Journal: Environ Int Date: 2018-02-06 Impact factor: 13.352
Authors: Gwen Tindula; Sudipta Kumer Mukherjee; Sheikh Muhammad Ekramullah; D M Arman; Subrata Kumar Biswas; Joynul Islam; John F Obrycki; David C Christiani; Liming Liang; Benjamin C Warf; Maitreyi Mazumdar Journal: Environ Int Date: 2021-08-03 Impact factor: 9.621
Authors: Richard H Finnell; Carlo Donato Caiaffa; Sung-Eun Kim; Yunping Lei; John Steele; Xuanye Cao; Gabriel Tukeman; Ying Linda Lin; Robert M Cabrera; Bogdan J Wlodarczyk Journal: Front Genet Date: 2021-05-10 Impact factor: 4.599