Kjersti Aagaard-Tillery1, Catherine Y Spong, Elizabeth Thom, Baha Sibai, George Wendel, Katharine Wenstrom, Philip Samuels, Hyagriv Simhan, Yoram Sorokin, Menachem Miodovnik, Paul Meis, Mary J O'Sullivan, Deborah Conway, Ronald J Wapner. 1. From the Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah; University of Tennessee, Memphis, Tennessee; University of Texas Southwestern Medical Center, Dallas, Texas; University of Alabama at Birmingham, Birmingham, Alabama; The Ohio State University, Columbus, Ohio; University of Pittsburgh, Pennsylvania; Wayne State University, Detroit, Michigan; University of Cincinnati, Cincinnati, Ohio; Wake Forest University Health Services, Winston-Salem, North Carolina; University of Miami, Miami, Florida; University of Texas at San Antonio, San Antonio, Texas; Thomas Jefferson University, Philadelphia, Pennsylvania; The George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute for Child Health and Human Development, Bethesda, Maryland.
Abstract
OBJECTIVE: To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke. METHODS: DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile462Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys160His T>A). Modification of the association between smoking and outcome by genotype was evaluated. Outcomes included birth weight, pregnancy loss, preterm birth, small for gestational age, and a composite outcome composed of the latter four components plus abruption. RESULTS: No interaction between maternal or fetal genotype of any of the polymorphisms and smoking could be demonstrated. In contrast, the association of smoking with gestational age-adjusted birth weight (birth weight ratio) was modified by fetal GSTT1 genotype (P for interaction=.02). Fetuses with GSTT1(del) had a mean birth weight reduction among smokers of 262 g (P=.01), whereas in fetuses without the GSTT1(del) the effect of tobacco exposure was nonsignificant (mean reduction 87 g, P=.16). After adjusting for confounding, results were similar. CONCLUSION: Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age-corrected birth weight.
OBJECTIVE: To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke. METHODS: DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile462Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys160His T>A). Modification of the association between smoking and outcome by genotype was evaluated. Outcomes included birth weight, pregnancy loss, preterm birth, small for gestational age, and a composite outcome composed of the latter four components plus abruption. RESULTS: No interaction between maternal or fetal genotype of any of the polymorphisms and smoking could be demonstrated. In contrast, the association of smoking with gestational age-adjusted birth weight (birth weight ratio) was modified by fetal GSTT1 genotype (P for interaction=.02). Fetuses with GSTT1(del) had a mean birth weight reduction among smokers of 262 g (P=.01), whereas in fetuses without the GSTT1(del) the effect of tobacco exposure was nonsignificant (mean reduction 87 g, P=.16). After adjusting for confounding, results were similar. CONCLUSION: Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age-corrected birth weight.
Authors: Kim M Smits; Simone Benhamou; Seymour Garte; Matty P Weijenberg; Yannis Alamanos; Christine Ambrosone; Herman Autrup; Judith L Autrup; Helena Baranova; Lisa Bathum; Paolo Boffetta; C Bouchardy; Jurgen Brockmoller; Dorota Butkiewicz; Ingolf Cascorbi; Margie L Clapper; Christiane Coutelle; Ann K Daly; Giacomo Muzi; Vita Dolzan; Tatyana G Duzhak; Katrin Farker; Klaus Golka; Aage Haugen; David W Hein; Allan Hildesheim; Ari Hirvonen; Ling L Hsieh; Magnus Ingelman-Sundberg; Ivan Kalina; Daehee Kang; Takahiko Katoh; Masahiro Kihara; Masako Ono-Kihara; Heon Kim; Chikako Kiyohara; Pierre Kremers; Philip Lazarus; Loic Le Marchand; Maria C Lechner; Stephanie London; Johannes J Manni; Christine M Maugard; Gareth J Morgan; Shunji Morita; Valle Nazar-Stewart; Vessela Nedelcheva Kristensen; Yoshio Oda; Fritz F Parl; Wilbert H M Peters; Agneta Rannug; Timothy Rebbeck; Luis F Ribeiro Pinto; Angela Risch; Marjorie Romkes; Jan Salagovic; Bernadette Schoket; Janeric Seidegard; Peter G Shields; Edith Sim; Daniel Sinnett; Richard C Strange; Isabelle Stucker; Haruhiko Sugimura; Jordi To-Figueras; Paolo Vineis; Mimi C Yu; Wei Zheng; Paola Pedotti; Emanuela Taioli Journal: Int J Cancer Date: 2004-06-10 Impact factor: 7.396
Authors: M Oscarson; R A McLellan; H Gullstén; J A Agúndez; J Benítez; A Rautio; H Raunio; O Pelkonen; M Ingelman-Sundberg Journal: FEBS Lett Date: 1999-10-29 Impact factor: 4.124
Authors: B C Gladen; T D Zadorozhnaja; N Chislovska; D O Hryhorczuk; M C Kennicutt; R E Little Journal: Hum Exp Toxicol Date: 2000-11 Impact factor: 2.903
Authors: Kjersti M Aagaard-Tillery; T Flint Porter; Robert H Lane; Michael W Varner; D Yvette Lacoursiere Journal: Am J Obstet Gynecol Date: 2008-01 Impact factor: 8.661
Authors: Melissa Suter; Jun Ma; Alan Harris; Lauren Patterson; Kathleen A Brown; Cynthia Shope; Lori Showalter; Adi Abramovici; Kjersti M Aagaard-Tillery Journal: Epigenetics Date: 2011-11-01 Impact factor: 4.528
Authors: Amber R Cooper; Kathleen E O'Neill; Jenifer E Allsworth; Emily S Jungheim; Anthony O Odibo; Diana L Gray; Valerie S Ratts; Kelle H Moley; Randall R Odem Journal: Fertil Steril Date: 2011-09-25 Impact factor: 7.329
Authors: Digna R Velez Edwards; Roberto Romero; Juan Pedro Kusanovic; Sonia S Hassan; Shali Mazaki-Tovi; Edi Vaisbuch; Chong Jai Kim; Offer Erez; Tinnakorn Chaiworapongsa; Brad D Pearce; Jacquelaine Bartlett; Lara A Friel; Benjamin A Salisbury; Madan Kumar Anant; Gerald F Vovis; Min Seob Lee; Ricardo Gomez; Ernesto Behnke; Enrique Oyarzun; Gerard Tromp; Ramkumar Menon; Scott M Williams Journal: J Matern Fetal Neonatal Med Date: 2010-07-09
Authors: Elena Sbrana; Melissa A Suter; Adi R Abramovici; Hal K Hawkins; Joan E Moss; Lauren Patterson; Cynthia Shope; Kjersti Aagaard-Tillery Journal: Am J Obstet Gynecol Date: 2011-06-15 Impact factor: 8.661