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Study: Boys face higher respiratory risk because of one less X chromosome

By Allen Cone
Human airways already demonstrate gender-based differences in DNA methylation signatures at birth, providing an early hint of which infants may be predisposed to develop respiratory disorders like asthma later in life, researchers say in a new study. Photo courtesy of Children's National Health System
Human airways already demonstrate gender-based differences in DNA methylation signatures at birth, providing an early hint of which infants may be predisposed to develop respiratory disorders like asthma later in life, researchers say in a new study. Photo courtesy of Children's National Health System

April 6 (UPI) -- Boys face a greater risk of respiratory problems, including asthma, later in life because they have only one gender-based X chromosome, according to a study, leading to possible personalized diagnostic and therapeutic approaches.

A multi-institution research team examined gender-based genetic signatures in the human airway early in children's lives, paying special attention to the DNA methylation patterns of the X chromosome. Their findings were published Tuesday in Scientific Reports.

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"It's clear as we round in the neonatal intensive care unit that baby boys remain hospitalized longer than girls and that respiratory ailments are quite common," Dr. Gustavo Nino, a pulmonologist at Children's National Health System in Washington, D.C., said in a press release. "Our work provides new insights about gender differences in airway disease risk that are pre-determined by genetics."

Respiratory conditions include bronchitis, pneumonia, croup and childhood asthma.

Asthma is the leading cause of chronic illness in children, and is more prevalent among boys, at 9.2 percent, than among girls, at 7.4 percent, according to the Centers for Disease Control and Prevention. This, despite asthma being more prevalent in women than men, the CDC reported.

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Girls have an additional copy of the X chromosome, which is enriched with immune-related genes, including those that play key roles in the development of respiratory conditions.

Although methylation prevents excessive gene activity in X-linked genes, much is unknown about how this process influences infants' risk of developing airway diseases, researchers said.

For the new study, nasal-wash samples were obtained from 12 newborns and infants up to 6 months old -- half born preterm and half full term -- who were admitted to Children's National Health System.

Using a gender classification algorithm to generate DNA methylation signals, the researchers identified X-linked genes with significant differences in methylation patterns in boys compared with girls.

In a separate group, they retrieved pediatric nasal airway epithelial cultures from a study that looked at genomic DNA methylation patterns and gene expression with persistent atopic asthma compared with healthy children. Each group included 36 African-American children between the ages of 10 and 12.

The researchers classified X-linked genes with significant gender-based X methylation and those genes whose X methylation was variable.

"These results confirm that the X chromosome contains crucial information about gender-related genetic differences in different airway tissues," Nino said. "More detailed knowledge of the genetic basis for gender differences in the respiratory system may help to predict, prevent and treat respiratory disorders that can affect patients over their entire lifetimes."

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The researchers are confident their finding can lead to better care for boys.

"Characterizing early airway methylation signatures holds the promise of clarifying the nature of gender-based disparities in respiratory disorders and could usher in more personalized diagnostic and therapeutic approaches," Nino said.

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