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Our aim was to examine the interaction terms of gene variants in biotransformation enzyme pathways and air pollution exposures in relation to risk of several structural birth defects. We evaluated the role of ambient air pollutant exposure (nitrogen dioxide [NO\n                    <jats:sub>2<\/jats:sub>\n                    ], nitrogen oxide, carbon monoxide, particulate matter &lt;10 [PM\n                    <jats:sub>10<\/jats:sub>\n                    ] and &lt;2.5 [PM\n                    <jats:sub>2.5<\/jats:sub>\n                    ] microns) during pregnancy and 104 gene variants of biotransformation enzymes from infant bloodspots or buccal cells in a California population\u2010based case\u2013control study in 1997\u20132006. Cases included cleft lip with or without cleft palate (\n                    <jats:italic>N<\/jats:italic>\n                    = 206), gastroschisis (\n                    <jats:italic>N<\/jats:italic>\n                    = 94), tetralogy of Fallot (\n                    <jats:italic>N<\/jats:italic>\n                    = 69), and dextro\u2010transposition of the great arteries (d\u2010TGA;\n                    <jats:italic>N<\/jats:italic>\n                    = 40) and were compared to 208 nonmalformed controls. Overall, the results were not consistent, though did highlight some associations for further investigation as indicated by Wald chi\u2010square test\n                    <jats:italic>p<\/jats:italic>\n                    value &lt;.1. Increased risk of cleft lip was associated with exposure to high PM\n                    <jats:sub>10<\/jats:sub>\n                    and two CYP gene variants. High PM\n                    <jats:sub>2.5<\/jats:sub>\n                    and the variant of\n                    <jats:italic>SLCO1B1<\/jats:italic>\n                    was associated with increased risk of teratology of Fallot. Higher NO\n                    <jats:sub>2<\/jats:sub>\n                    and two gene variants,\n                    <jats:italic>CYP2A6<\/jats:italic>\n                    and\n                    <jats:italic>SLC01B1<\/jats:italic>\n                    , were associated with increased risk of d\u2010TGA. Results for gastroschisis were inconsistent in direction and across pollutants. These exploratory results suggest that some individuals based on their genetic background may be more susceptible to the adverse effects of air pollution.\n                  <\/jats:p>","DOI":"10.1002\/bdr2.1880","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T01:56:32Z","timestamp":1613008592000},"page":"676-686","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Gene\u2013environment interactions between air pollution and biotransformation enzymes and risk of birth defects"],"prefix":"10.1002","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1435-4814","authenticated-orcid":false,"given":"Amy M.","family":"Padula","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Schultz","sequence":"additional","affiliation":[{"name":"San Francisco Benioff Children's Hospital Oakland, University of California  Oakland California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Lee","sequence":"additional","affiliation":[{"name":"San Francisco Benioff Children's Hospital Oakland, University of California  Oakland California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Lurmann","sequence":"additional","affiliation":[{"name":"Sonoma Technology Inc.  Petaluma California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Katharine","family":"Hammond","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences University of California  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7438-4914","authenticated-orcid":false,"given":"Gary M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.06.028"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3016.1991.tb00728.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2020.126668"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36478"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.6065"},{"issue":"2","key":"e_1_2_8_8_1","first-page":"265","article-title":"Polymorphisms in drug\u2010metabolizing enzymes: What is their clinical relevance and why do they exist?","volume":"60","author":"Nebert D. 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