Maternal Telomere Length and Risk of Down Syndrome: Epidemiological Impact of Smokeless Chewing Tobacco and Oral Contraceptive on Segregation of Chromosome 21

Abstract

Background: We have previously demonstrated a relationship between children born with Down syndrome and maternal telomere length. Similarly, exposure to tobacco and oral contraceptives has been explored in one of our earlier studies as a risk factor for Down syndrome. Objective: In the present study, we consider the interactions among these risk factors associated with Down syndrome in a population from Kolkata, India, using analyses stratified by maternal age. Methods: We estimated the telomere length of women with children with Down syndrome by restriction enzyme/Southern blot methods. Linear regression was employed to estimate telomere shortening as an indicator of the maternal age of conception. Interactions among the various factors were analyzed by logistic regression. Result: We found an association between the use of smokeless chewing tobacco and shorter telomere length among women who experienced meiosis I nondisjunction at gametogenesis; the effect is seen across all maternal age groups. In contrast, oral contraceptive use alone did not exhibit a statistically significant association with maternal telomere length, but there was an interaction with the use of smokeless chewing tobacco in the older mothers who experienced meiotic II nondisjunction. Conclusion: Environmental/habitual factors interact with molecular components of the oocyte, which ultimately increases the risk of chromosome 21 nondisjunction and subsequently of giving birth to a child with Down syndrome.