4 March 2013

Can nicotine transmit disease through multiple generations?

by Will Parker

Nicotine creates heritable epigenetic marks on the genome, say Los Angeles Biomedical Research Institute scientists who contend that a grandparent's smoking habits may be responsible for asthma and other respiratory conditions in grandchildren. Their controversial take on epigenetics (where an environmental factor causes a genetic change), appearing in the Review of Obstetrics & Gynecology, further suggests that environmental factors experienced today could determine the health of family members for generations to come.

The authors of the paper, John S. Torday and Virender K. Rehan, based their work on recent studies by Rehan that showed pregnant rats given nicotine produced asthmatic pups that went on to produce their own asthmatic pups, despite the absence of nicotine exposure in the third generation. The findings suggest nicotine can leave heritable epigenetic marks on the genome, which make future offspring more susceptible to respiratory conditions.

Rehan said that nicotine affects both the lung cells and the sex cells in ways that caused the lungs that developed from those cells to develop abnormally, causing asthma. "The functional effects of nicotine on the offspring were accompanied by increased expression of contractile proteins in the whole lung, as well as in fibroblasts isolated from the lung, accompanied by decreased expression of certain proteins," he explained.

Torday added that such alterations in specific developmental and maturational programs are subtle, explaining significant long-term adverse pulmonary outcomes, but relatively minor immediate effects.

The researchers also cited the Children's Health Study from Southern California, which found that grandmaternal smoking during pregnancy increases the risk of asthma in grandchildren - regardless of whether the mother smoked or not.

Based on those findings and Rehan's earlier work, the researchers conclude that environmental factors experienced during pregnancy will affect not only the child in utero but also future generations of the same family. They say this multi-generational transmission could explain why nearly all of inherited human diseases are unaccounted for by the prevailing model of Mendelian genetic trait transmission.

"The transmission of asthma to the second generation and its prevention by a specifically-targeted molecular intervention are the first unequivocal demonstrations of multi-generational transmission of an epigenetically-mediated effect on the offspring," Torday said.

The researchers also note that since nicotine affects nicotinic receptors in the muscle of both airways and the uterus, it may explain the relationship between hyper-reactive airways and preterm birth. Rehan concludes with the tantalizing notion that various epigenetic alterations might be prevented by targeted molecular interventions.

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Source: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)