BACKGROUND: Maternal smoking is a known risk factor for orofacial clefts. We investigated whether risk is greater among offspring who lack the genetic capacity to produce glutathione S-transferase enzymes relevant to detoxification of chemicals in cigarette smoke. METHODS: Using a population-based case-control design, we genotyped 423 California infants with an isolated cleft and 294 nonmalformed controls for null variants of the glutathione S-transferases GSTT1 and GSTM1. RESULTS: If a mother smoked during pregnancy and her fetus was homozygous null for GSTT1, the risk of isolated cleft lip with or without cleft palate was tripled (odds ratio = 2.9; 95% confidence interval = 1.2-7.2). For fetuses who were homozygous null for GSTM1 and whose mothers smoked >/=20 cigarettes per day, we found nearly a 7-fold increased risk (6.8; 0.82-57). Combined absence of GSTM1 and GSTT1 enzymes among the offspring of smoking mothers was associated with a nearly 6-fold increased risk for cleft lip (6.3; 1.3-42). A similar increased risk for cleft palate was associated with absence of GSTM1, but not for absence of GSTT1. CONCLUSIONS: Maternal smoking during pregnancy increases risks for clefts among fetuses lacking enzymes involved in the detoxification of tobacco-derived chemicals.
BACKGROUND: Maternal smoking is a known risk factor for orofacial clefts. We investigated whether risk is greater among offspring who lack the genetic capacity to produce glutathione S-transferase enzymes relevant to detoxification of chemicals in cigarette smoke. METHODS: Using a population-based case-control design, we genotyped 423 California infants with an isolated cleft and 294 nonmalformed controls for null variants of the glutathione S-transferases GSTT1 and GSTM1. RESULTS: If a mother smoked during pregnancy and her fetus was homozygous null for GSTT1, the risk of isolated cleft lip with or without cleft palate was tripled (odds ratio = 2.9; 95% confidence interval = 1.2-7.2). For fetuses who were homozygous null for GSTM1 and whose mothers smoked >/=20 cigarettes per day, we found nearly a 7-fold increased risk (6.8; 0.82-57). Combined absence of GSTM1 and GSTT1 enzymes among the offspring of smoking mothers was associated with a nearly 6-fold increased risk for cleft lip (6.3; 1.3-42). A similar increased risk for cleft palate was associated with absence of GSTM1, but not for absence of GSTT1. CONCLUSIONS: Maternal smoking during pregnancy increases risks for clefts among fetuses lacking enzymes involved in the detoxification of tobacco-derived chemicals.
Authors: Jenna C Carlson; Nichole L Nidey; Azeez Butali; Carmen J Buxo; Kaare Christensen; Frederic W-D Deleyiannis; Jacqueline T Hecht; L Leigh Field; Lina M Moreno-Uribe; Ieda M Orioli; Fernando A Poletta; Carmencita Padilla; Alexandre R Vieira; Seth M Weinberg; George L Wehby; Eleanor Feingold; Jeffrey C Murray; Mary L Marazita; Elizabeth J Leslie Journal: Genet Epidemiol Date: 2018-09-11 Impact factor: 2.135
Authors: Lina M Moreno; Maria Adela Mansilla; Steve A Bullard; Margaret E Cooper; Tamara D Busch; Junichiro Machida; Marla K Johnson; David Brauer; Katherine Krahn; Sandy Daack-Hirsch; Jamie L'heureux; Consuelo Valencia-Ramirez; Dora Rivera; Ana Maria López; Manuel A Moreno; Anne Hing; Edward J Lammer; Marilyn Jones; Kaare Christensen; Rolv T Lie; Astanand Jugessur; Allen J Wilcox; Peter Chines; Elizabeth Pugh; Kim Doheny; Mauricio Arcos-Burgos; Mary L Marazita; Jeffrey C Murray; Andrew C Lidral Journal: Hum Mol Genet Date: 2009-09-24 Impact factor: 6.150