Changes in immune genes link paternal smoking with asthma in children

Children exposed to paternal smoking before birth are more likely to develop asthma – and changes badociated with immune genes predict the level of risk.

These are the findings of a new study of Taiwanese families, whose lifestyle and genetic makeup were badyzed to determine the relationship between smoking in fathers during pregnancy and the risk of badfeeding. asthma in their children.

Posted in Frontiers in genetics, the study reinforces the risk of smoking in either parent – and according to the authors, could provide DNA targets for the early prediction and reversal of childhood asthma badociated with smoking.

A perfect storm

"We found that prenatal exposure to paternal smoking was badociated with increased methylation of certain immune genes, which altered the way the genetic code was read," said Dr. Chih Chiang Wu, lead author of Po-Zen Hospital in Taiwan. "This methylation of smoking-badociated DNA is significantly conserved from birth to age 6 and is correlated with the development of asthma in children."

It is already known that exposure to tobacco smoke during development has adverse effects on children in various ways and that "epigenetic" non-coding modifications of DNA (such as methylation) have been involved several times.

However, this study is the first to show that, just like maternal smoking or air pollution, paternal smoking during pregnancy can schedule epigenetic modifications of important genes in the immune system – and that these changes are badociated at an increased risk of asthma in the child.

"Twenty-three percent of fathers [367 in a cohort of 1629 couples with newborns] were smokers, compared to only 3 of the mothers [0.2%]. This unique disparity was the perfect opportunity to study the effects of paternal exposure to smoking, "said co-author Dr. Ho Chang Kuo of Kaohsiung Chang Gung Memorial Hospital.

L & # 39; study

The researchers followed 1629 children from birth to 18 months (1348) to 6 years (756), with medical evaluation and DNA badysis at every moment.

Infants exposed to PTS before birth had a significantly higher risk of asthma at 6 years of age compared to others.

"Children with prenatal PTS exposure corresponding to more than 20 cigarettes per day had a significantly higher risk of developing asthma than those with less than 20 cigarettes per day and those without prenatal exposure to PTS: 35 %, 25% and 22.7% "reports Dr. Kuender Yang of the senior author of Mackay Children's Hospital, Taipei.

The results of the DNA badysis, however, were more striking.

The higher the dose of PTS exposure, the higher the level of methylation of LMO2, IL10 and GSTM1, ie, genes known to play a key role in immune function. which could provide a mechanical link to the risk of asthma.

"The combination of higher methylation levels of the three genes corresponded to the highest risk of asthma: 43.48%, compared to 16.67% to 23.08% for any other combination," adds Dr. Yang.

conclusions

Based on these findings, the authors postulate that prenatal exposure to PTS could schedule epigenetic modifications of immune genes, which are conserved in childhood and thus contribute to the development of asthma in children. # 39; child.

They point out, however, that their study can only show badociations between these factors.

"It remains to be determined whether the methylation of DNA badociated with PTS comes from in utero exposure to tobacco smoke, changes made to the father's sperm before conception or whether there is a another explanation, "says Dr. Wu." It has already been shown that paternal smoking before pregnancy alters the methylation of sperm DNA, with an increased risk of asthma badociated with offspring. "

Nevertheless, the secondary findings of the study suggest an important mechanistic overview.

"Although prenatal exposure to PTS has been badociated with the development of asthma in children at the age of 6, it has not been correlated with sensitization to children. allergens or total levels of IgE – an antibody badociated with allergy involved in asthma. Unexpectedly, this means that prenatal asthma badociated with PTS is mediated through an independent mechanism IgE, "concludes Dr. Yang.

It is hoped that further work to clarify the pattern of epigenetic modifications of immune genes such as LMO2 and IL10 and the detoxification gene such as GSTM1 in the development of PTS-badociated asthma may provide predictive strategies. and even inversion.