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Genetic Marker May Flag Risk Of Asthma, Poor Lung Function


 

A protein linked to inflammation and tissue remodeling is a significant biomarker for asthma and poor lung function, and a variation in that protein's genetic code is also associated with asthma risk and bronchial hyperresponsiveness.

A single-nucleotide polymorphism (SNP) was associated with elevated serum levels of the protein, YKL-40, in several populations, and both the genetic variation and elevated YKL-40 levels were associated with asthma, bronchial hyperresponsiveness, and reduced lung function, according to Carol Ober, Ph.D., of the University of Chicago and her associates in the United States and Germany (N. Engl. J. Med. 2008;358:1682–91).

In an earlier study, some of the same investigators had reported that serum levels of YKL-40 were elevated in patients with asthma. Serum YKL-40 levels also were associated with asthma severity, thickness of the subepithelial basement membrane, and pulmonary function, suggesting that YKL-40 levels could be a biomarker for asthma.

The investigators conducted a genomewide association study in a group of 632 related Hutterites aged 6–92 years (mean age 33) living on communal farms in South Dakota. They also included studies of children with and without asthma.

The Hutterites' mean YKL-40 levels were 15% higher among those with asthma and 10% higher among those with bronchial hyperresponsiveness, compared with controls. They also found a significant association between an SNP in CHI3L1, a gene encoding for YKL-40, and elevated serum YKL-40 levels, asthma, bronchial hyperresponsiveness, and measures of pulmonary function.

The researchers also determined that the same SNP was predictive of asthma from birth through age 5 years in a study of 638 German children at about age 10 years, and in a study of 296 adults and children in Chicago.

The result “shows that serum YKL-40 level is a highly heritable, quantitative trait in humans and confirms that YKL-40 is a significant biomarker for asthma susceptibility and reduced lung function,” the authors wrote. Genetic variation in CHI3L1 “influences serum YKL-40 levels and is associated with the risk of asthma, bronchial hyperresponsiveness, and reduced lung function.”

Identifying the rest of the genetic loci that contribute to the differences in serum YKL-40 levels and related proteins “could identify additional genes with a significant effect on the risk of asthma and lung function,” the researchers added.

These results need to be confirmed with large studies, Miriam Moffatt, D.Phil., and Dr. William O.C.M. Cookson of the National Heart and Lung Institute at Imperial College London, said in an accompanying editorial (N. Engl. J. Med. 2008;358:1725–6).

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