A tiny variation in a gene known as CHI3L1 increases susceptibility to asthma, bronchial hyperresponsiveness, and decline in lung function, researchers report online in the New England Journal of Medicine. The print version will appear in the April 17 issue.

The gene variant causes increased blood levels of YKL-40, a biomarker for asthma. A slightly different version of the genetic variation lowers YKL-40 levels and protects against asthma.

Though the original discovery came from a study of a genetically isolated population, the Hutterites of South Dakota, the researchers were able to confirm the same connections between the CHI3L1 variations, YKL-40 levels, and asthma susceptibility in three genetically diverse Caucasian populations from Chicago; Madison, Wisconsin; and Freiberg, Germany.

"This is exciting because it connects asthma susceptibility to a whole new pathway at the protein and the genetic levels," said study author Carole Ober, professor of human genetics at the University of Chicago Medical Center. "There is a good deal more we need to find out about this connection, but now we know where to look.

Ober and colleagues at the University of Chicago had long been searching for genetic factors that could influence the risk of common diseases, such as asthma. They have focused since 1994 on the Hutterites, a genetically isolated US religious community descended from about 90 people, which immigrated to the United States in 1874 and settled in small communal farming colonies in what is now South Dakota.