Scientists supported by the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health, report that women who smoke during pregnancy and carry a fetus whose DNA lacks both copies of a gene involved in detoxifying cigarette smoke substantially increase their baby's chances of being born with a cleft lip and/or palate.
According to the scientists, about a quarter of babies of European ancestry and possibly up to 60 percent of those of Asian ancestry lack both copies of the gene called GSTT1. Based on their data, published in the January issue of the American Journal of Human Genetics, the scientists calculated that if a pregnant woman smokes 15 cigarettes or more per day, the chances of her GSTT1-lacking fetus developing a cleft increase nearly 20 fold. Globally, about 12 million women each year smoke through their pregnancies.
Dr. Jeff Murray, a scientist at the University of Iowa and senior author of the study, noted that parents who are considering having a child and need added motivation for the mother to quit smoking might one day be tested to determine their GSTT1 status. Because the fetus inherits its genes from both mother and father, the test would determine the likelihood of the baby developing without the GSTT1 gene to detoxify the cigarette smoke.
"A test that indicates the GSTT1 gene is present certainly would not eliminate a baby's risk of a cleft because many other genetic and environmental factors can be involved." said Murray. "But the opposite result would give the mother one more compelling reason to quit smoking for her own health and for the sake of her child."
In the United States, about one in every 750 babies is born with isolated, also called nonsyndromic, cleft lip and/or palate. The condition is correctable but typically requires several surgeries. Families often undergo tremendous emotional and economic hardship during the process, and children frequently require many other services, including complex dental care and speech therapy.
According to Murray, researchers have built a strong statistical case over the past several years that pregnant women who smoke put their unborn babies at greater risk of developing a cleft. The data raised two related questions. "Do genetic variations in the mother influence her own metabolism of the cigarette smoke and its byproducts, thus setting in motion developmental changes that cause the cleft in the fetus? Or do genetic variations in the fetus itself compromise its ability to metabolize the cigarette smoke and cause the cleft?" said Dr. Min Shi, now a scientist at NIH's National Institute of Environmental Health Sciences and a lead author of the paper.
To find the answers, Murray's group teamed with colleagues in Denmark to perform a large, complex, and possibly first-of-its-kind international study. The group first assembled a list of 16 genes of interest, each of which encode proteins that plug into various pathways in the body involved in detoxifying dangerous chemicals. "We picked genes that previous evidence shows either are directly involved in cigarette smoke toxicity or are major players in general toxicity management in people," said Dr. Kaare Christensen, a scientist at the University of Southern Denmark in Odense and an author on the paper.