17q21: Gene Variations, Secondhand Smoke Linked to Early Asthma, espec for children under 4

[Guest guest]

nejm article-link follows the news item. Not long ago, a peer-reviewed

study affirmed an association between asthma and certain vaccinations.

Gradually, genetic risk-factors are recognized. When will

pre-vaccination screening become normal procedure - or at least

parent-paid procedure. Eg, prior to an infant's first vaccination

incident, the parents might request genomic testing to rule out alleles

increasing risk for *known* adverse effects.

- - - -

Gene Variations, Secondhand Smoke Linked to Early Asthma

The combination nearly tripled the risk for children under 4, study found

By Gardner

HealthDay Reporter

http://healthday.com/Article.asp?AID=620336

WEDNESDAY, Oct. 15 (HealthDay News) -- Certain genetic variations

previously identified as putting people at higher risk for asthma

apparently only increase the risk of so-called early-onset asthma, which

is disease that appears at 4 years of age or younger.

The risk is further increased by exposure to secondhand smoke, again

early in life, according to a study in the Oct. 16 issue of the New

England Journal of Medicine.

" This helps support the theory that asthma is not a uniform disease.

It's probably several problems that end up with the same type of

symptoms, " said Dr. Leath, assistant professor of pediatrics at

the Texas A & M Health Science Center College of Medicine. " It also

supports the fact that it's not just genes that cause asthma, and it's

not just the environment, but the interaction between the two. "

Another striking point in the study was the clear cut-off point of 4

years of age, experts said.

" It seems clear that there are certain genetic loci that are connected

with early onset asthma -- that wasn't surprising, " said Dr. Len

Horovitz, a pulmonary specialist with Lenox Hill Hospital in New York

City. " What was interesting was the interlude between nature and

nurture. It's clear that those kids exposed to secondhand smoke had much

more of a flowering of the disease process than those who weren't. That

illustrates that while something can be genetically determined, it can

be amplified by environmental factors. "

Even so, the study results won't have any immediate clinical

implications, said Leath, adding, " It's a great step in the right

direction, but we don't know what to do with it. "

Asthma is increasingly recognized as a number of separate diseases,

rather than one, overarching disease. Not much is known about the causes

of different forms of the respiratory condition, and understanding the

causes could help unravel the biological mechanisms behind the disease

processes.

The age at which asthma begins is one way to differentiate different

types -- or " phenotypes " -- of the disease.

A previous, genome-wide association study found that genetic variations

at chromosome 17q21 were linked to a heightened risk of asthma. But it

wasn't known if these variations (also known as single-nucleotide

polymorphisms, or SNPs) had a connection with the age at which asthma

developed.

For the new study, French researchers tested 36 SNPs in the 17q21 region

among 1,511 people from 372 families.

Eleven SNPs were " significantly associated " with asthma, and three of

those were " strongly associated " with the disease. Four SNPs were

strongly associated with early onset asthma but had no relationship with

late-onset disease.

There was an even stronger association between six variants and asthma

in people who had been exposed to secondhand smoke at an early age -- an

almost threefold increase in risk in children with the genetic variant

and early exposure to smoke.

The study's lead author, Dr. Florence Demenais, noted, " Our findings can

provide a greater understanding of the role of the 17q21 genetic

variants in the pathophysiology of asthma. Indeed, we found that their

effect is restricted to early-onset asthma (occurring at 4 years of age

or younger). "

Demenais, director of research at INSERM (the French National Institute

of Health and Medical Research) in Paris, added, " The risk of

early-onset asthma conferred by these variants is enhanced when the

subjects have been exposed to environmental tobacco smoke in early life.

These variants regulate the expression of at least two genes, ORMDL3 and

GSDML (also called GSDMB). "

SOURCES: Florence Demenais, M.D., director of research, INSERM (French

National Institute of Health and Medical Research), Paris; Len Horovitz,

M.D., pulmonary specialist, Lenox Hill Hospital, New York City;

Leath, M.D., assistant professor of pediatrics, Texas A & M Health Science

Center College of Medicine, and pediatrician, & White Round Rock

University Medical Campus, Round Rock, Texas; Oct. 16, 2008, New England

Journal of Medicine

Last Updated: Oct. 15, 2008

Copyright © 2008 ScoutNews, LLC. All rights reserved.

Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma

<http://content.nejm.org/cgi/content/full/NEJMoa0806604>

A locus on chromosome 17 has previously been shown to be associated with

susceptibility to asthma. This study shows that the association is

specific to early-onset asthma (occurring at the age of 4 years or

younger) in those exposed to environmental tobacco smoke in early life.