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Vol. LXIII, No. 21
October 14, 2011
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Digest

NIH-Funded Study Connects Gene Variant to Response to Asthma Drugs

A genetic variant may explain why some people with asthma do not respond well to inhaled corticosteroids, the most widely prescribed medicine for long-term asthma control.
A genetic variant may explain why some people with asthma do not respond well to inhaled corticosteroids, the most widely prescribed medicine for long-term asthma control.

A genetic variant may explain why some people with asthma do not respond well to inhaled corticosteroids, the most widely prescribed medicine for long-term asthma control. Researchers found that asthma patients who have two copies of a specific gene variant responded only one-third as well to steroid inhalers as those with two copies of the regular gene.

This genome-wide association study, funded by NHLBI, analyzed data from over 1,000 people enrolled in five separate clinical trials that studied different steroid treatments for asthma. The study was also funded by NHGRI and the NIH Pharmacogenomics Research Network. The results appeared in the Sept. 26 online edition of the New England Journal of Medicine.

“This finding helps to explain the genetic basis for the long-standing observation that some people do not respond well to what is a common asthma treatment,” said Dr. Susan Shurin, acting NHLBI director. “The study illustrates the importance of research examining the relationship between genetic makeup and response to therapy for asthma and underscores the need for personalized treatment for those who have it.”

New Technique Identifies First Events in Tumor Development

A novel technique that enables scientists to measure and document tumor-inducing changes in DNA is providing new insight into the earliest events involved in the formation of leukemias, lymphomas and sarcomas and could potentially lead to the discovery of ways to stop those events.

Developed by a team of researchers at NIAMS, NCI and Rockefeller University, the technology focuses on chromosomal rearrangements known as translocations. Translocations occur when a broken strand of DNA from one chromosome is erroneously joined with that of another chromosome. Sometimes these irregularities can be beneficial in that they enable the immune system to respond to a vast number of microorganisms and viruses. However, translocations can also result in tumors.

The findings were reported in the Sept. 30 issue of the journal Cell.

Translocations can take place during the course of normal cell division, when each chromosome—“ a single strand of DNA containing many genes”—is copied verbatim to provide genetic information for the daughter cells. Sometimes, during this process, byproducts of normal metabolism or other factors can cause breaks in the DNA.

“The cell expresses specific enzymes whose primary purpose is to repair such lesions effectively, but when the enzymes mistakenly join pieces of two different chromosomes, the cell’s genetic information is changed,” said NIAMS’s Dr. Rafael Casellas. He likens the phenomenon to breaking two sentences and then rejoining them incorrectly. For example, “The boy completed his homework.” and “The dog went to the vet.” might become “The dog completed his homework.” or “The boy went to the vet.” When a cell gets nonsensical information such as this, it can become deregulated and even malignant.

Genetic Mutation Linked to Inherited Forms of ALS, Dementia

NIH scientists and worldwide teams of researchers have identified the most common genetic cause known to date for two neurological diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The discovery offers clues to underlying mechanisms of these diseases and may eventually contribute to the design and testing of possible therapies. The research results appeared online in Neuron on Sept. 21.

Researchers found that a mutation on a single gene, C9ORF72 on the short arm of chromosome 9, accounts for nearly 50 percent of the directly inherited, familial ALS and FTD in the Finnish population and more than a third of familial ALS in other groups of European ancestry. The mutation, called a hexanucleotide repeat expansion, is an unusual one that involves repeating a DNA sequence over and over again. The researchers also found these mutations in Finnish people with the more common, sporadic form of ALS.

“Identifying this defective gene common to both the inherited forms of ALS and FTD and the sporadic form of ALS provides important new insights into the development of these neurodegenerative diseases,” said NIA director Dr. Richard Hodes. “We still have much to learn about the complex interplay between genetic risk for a disorder and the other factors that determine disease onset and progression. But finding these types of mutations is critically important to a better understanding of disease mechanisms so that we can ultimately target disease biology to develop therapeutics.”


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