title: Epidemiology of Down syndrome: new insight into the multidimensional interactions among genetic and environmental risk factors in the oocyte.
abstract: Down syndrome birth is attributable to multiple maternal risk factors that include both genetic and environmental challenges, but there is limited understanding of the complicated interactions among these factors. In the present study, a case-control analysis of approximately 400 infants with or without suspected Down syndrome reported between 2003 and 2009 and their parents in and around Kolkata, India, was conducted. Maternal exposure to 2 environmental risk factors (smokeless chewing tobacco and oral contraceptive pills) was recorded, and families were genotyped with microsatellite markers to establish the origin of nondisjunction errors as well as recombination patterns of nondisjoined chromosome 21. With logistic regression models, the possible interactions among all of these risk factors, as well as with maternal age, were explored. Smokeless chewing tobacco was associated with significant risk for meiosis II nondisjunction and achiasmate (nonexchange) meiosis I error among young mothers. By contrast, the risk due to oral contraceptive pills was associated with older mothers. Study results suggest that the chewing tobacco risk factor operates independently of the maternal age effect, whereas contraceptive pill-related risk may interact with or exacerbate age-related risk. Moreover, both risk factors, when present together, exhibited a strong age-dependent effect.
authors.affiliation: Human Genetics Research Unit, Department of Biotechnology, School of Biotechnology and Biological Sciences, West Bengal University of Technology, Salt Lake City, Kolkata, West Bengal, India.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.forename: Chang-Sook
authors.initials: CS
authors.lastname: Hong
authors.forename: Eleanor
authors.initials: E
authors.lastname: Feingold
authors.forename: Papiya
authors.initials: P
authors.lastname: Ghosh
authors.forename: Priyanka
authors.initials: P
authors.lastname: Ghosh
authors.forename: Pranami
authors.initials: P
authors.lastname: Bhaumik
authors.forename: Subrata Kumar
authors.initials: SK
authors.lastname: Dey
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000009:adverse effects; D004314:Down Syndrome / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D016015:Logistic Models; D008423:Maternal Age; D018895:Microsatellite Repeats / Q000235:genetics; D009630:Nondisjunction, Genetic / Q000235:genetics; D009865:Oocytes / Q000187:drug effects*; D012307:Risk Factors; D014030:Tobacco, Smokeless / Q000009:adverse effects
chemical_list: D003276:Contraceptives, Oral