Limb deficiency defects, MSX1, and exposure to tobacco smoke.
There is increasing evidence from epidemiologic studies that genetic susceptibilities may modify the teratogenic effects of smoking. A previous study suggested that maternal smoking in the presence of a dinucleotide repeat polymorphism for MSX1 produced an almost fivefold increased risk for limb anomalies, providing evidence for a gene-environment interaction. The current study examined this potential interaction, using case-control data with several methodologic improvements, including a larger sample size and more detailed information on cigarette smoke exposures. Cases (n = 92) were ascertained from pregnancies ending in 1987-1989, and controls (n = 180) were randomly selected from eligible liveborn infants. In telephone interviews, women reported smoking behaviors during the month before pregnancy through the end of the first trimester. Odds ratios (OR) for maternal and paternal smoking ranged from 1.0 to 1.4, risk estimates were imprecise; for example, the OR for maternal smoking >or=20 cigarettes per day, versus none, was 1.3 (95% confidence interval (CI) 0.5-3.4). Relative to the homozygous wildtype, the OR was 1.5 (95% CI 0.7-3.5) for the homozygous variant genotype and 0.8 (95% CI 0.5-1.4) for the heterozygous variant genotype. There was no evidence that maternal smoking or both parents smoking, in combination with a susceptible MSX1 genotype, conferred an additional increase in risk of limb defects. This study did not find a gene-environment interaction between maternal smoking, infant MSX1 CA repeat polymorphism, and risk of limb deficiency defects. This finding contrasts with results of a previous study, which provided initial evidence for such an interaction. Several important methodological differences may have contributed to the differences in findings between the two studies.
March of Dimes Birth Defect Foundation/California Department of Health Services, California Birth Defects Monitoring Program, Oakland, California 94710, USA. sca@cbdmp.org
Suzan L
SL
Carmichael
Gary M
GM
Shaw
Wei
W
Yang
Edward J
EJ
Lammer
Huiping
H
Zhu
Richard H
RH
Finnell
D000328:Adult; D016022:Case-Control Studies; D002675:Child, Preschool; D018900:Dinucleotide Repeats / Q000235:genetics*; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000453:epidemiology / Q000235:genetics*; D051957:MSX1 Transcription Factor; D008297:Male; D018811:Maternal Exposure; D016017:Odds Ratio; D018812:Paternal Exposure; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D014028:Tobacco Smoke Pollution
D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C484083:MSX1 protein, human; D014028:Tobacco Smoke Pollution