Scientists have known that cleft palate—a birth defect where the baby’s roof of the mouth does not form properly—is caused by certain genes and environmental factors. Maternal smoking during pregnancy has been implicated with cleft palate in babies. Recently, Wu and colleagues discovered two genes from chromosome 4 among Asians—predominantly East Asians—result in a higher risk of nonsyndromic cleft palate when mothers were exposed to tobacco smoke three months prior to pregnancy until the first trimester.
These results highlight the importance of incorporating environmental exposure with genetic analyses as many genes associated with cleft palate may otherwise be overlooked.
Nonsyndromic cleft palate occurs in 1 in every 2500 births and is one of the most common birth defects worldwide. About half of all cleft palate cases are nonsyndromic: those that are not accompanied with any other defects.
To decipher how both environmental exposure and genes interact, researchers conducted a genome-wide association study where they screened the genomes of 550 parents along with their children—known as case-parent trios. Mothers were surveyed through questionnaires about their lifestyle: cigarette smoking, alcohol consumption, exposure to tobacco smoke, and multivitamin supplementation. Since only 4 percent of Asian mothers smoked, they focused on exposure to tobacco smoke and multivitamin supplementation, which were 40.3 and 20.2 percent respectively.
The researchers then classified the 550 case-parent trios into ancestries—Asian or European—and compared them to find single letter variations in genes called single nucleotide polymorphisms or SNPs that are associated with maternal tobacco smoke exposure in either group.
When analyzed in isolation, none of the SNPs were significant. However, when they scrutinized them with respect to their interaction with environmental exposure, they revealed increased risk among the Asian group, which comprised 259 trios; this risk was attributed to multiple SNPs in two genes located in chromosome 4—SLC2A9 and WDR1.
For SLC2A9, the group identified 15 SNPs that confer a greater risk of nonsyndromic cleft palate of up to 2.58 times compared with that of unexposed mothers. Similarly, for WDR1, 9 SNPs were found to increase the risk of having a baby with cleft palate up to 2.75 times among exposed mothers.
Considering the high rate of smoke exposure among Asian women in this study (40.3%), these results suggest that mothers should avoid exposure to tobacco smoke in the months leading up to pregnancy as well as during the first trimester to protect their babies from this birth defect.
Without incorporating the exposure to tobacco into the genetic analysis, these genes would have been overlooked entirely. But the authors caution that larger scale studies are required to confirm the association and the exact gene locations.
Wu T, Schwender H, Ruczinski I, Murray JC, Marazita ML, et al. (2014) Evidence of Gene−Environment Interaction for Two Genes on Chromosome 4 and Environmental Tobacco Smoke in Controlling the Risk of Nonsyndromic Cleft Palate. PLoS ONE 9(2): e88088. doi:10.1371/journal.pone.0088088