Damaged genes linked to mothers who smoke

Two genes involved in metabolizing toxins from cigarettes apparently lead to low birth weight in newborns whose mothers smoke, providing a rare glimpse into the interplay between genes and smoking, researchers will report Wednesday.

Doctors have long known about the danger of smoking during pregnancy and have cautioned pregnant women to stop. Low birth weight is a major consequence of maternal smoking. But doctors have also observed that some smokers produce low birth weight babies while others do not.

In the medical analysis to be reported on Wednesday, it appears that the two genes, one dubbed CYP1A1 and the other called GSTT1, govern the risk of low birth weight. Both genes are involved in the chemical breakdown of poisons from cigarettes. Tobacco, previous studies have shown, contains more than 4,000 toxins. The most lethal -- because they also figure in lung cancer -- are polycyclic aromatic hydrocarbons, arylmines, and N-nitrosamines, all of which are inhaled in a single drag on a cigarette.

"Our data demonstrate that a subgroup of pregnant women with certain genotypes appeared to be particularly susceptible to the adverse effects of cigarette smoke," said Dr. Xioabin Wang, an associate professor at Boston University's medical school and an attending pediatrician at Boston University Medical Center.

Reporting in the Journal of the American Medical Association, Wang and her team examined 741 women in the three months before pregnancy and then in the first, second and third trimesters of the babies' development. The mothers-to-be were divided into groups of those who never smoked, and those who smoked any number of cigarettes during any one of the four periods.

The linchpin of the analysis was determining the women's genetic profiles and to assess how those genes affected the ultimate birth weight of the infants.

As with any genetic profiling there can be more than one genotype, even when the same genes are considered.

Individuals can be dominant or recessive for a trait, or they may not possess the gene at all. For instance, there was an increased risk of low birth weight with the CYP1A1 genotype, whether women were dominant or recessive for the trait. For some smokers with the trait, the increased risk of producing a low birth weight baby was 30 percent.

The increased risk of low birth weight for some women with the other gene, GSTT1, was as high as 70 percent in smokers.

Wang said the standard definition of low birth weight was used, which is defined as 2,500 grams or lower, which translates into any birth weight of 5 pounds, 8 ounces or less.

The thrust of the study was not to produce a way to screen for the two genes -- scientists are not planning to produce such a test. What is needed, Wang said, is better interventions to break the smoking habit, especially in pregnant women.