October 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. Thomas 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; Thomas Leath, M.D., assistant professor of pediatrics, Texas A&M Health Science Center College of Medicine, and pediatrician, Scott & White Round Rock University Medical Campus, Round Rock, Texas; Oct. 16, 2008, New England Journal of Medicine