BALTIMORE—A team of researchers from The Johns Hopkins University made an important advance in our understanding of the genetics of asthma recently when they showed that genes on different chromosomes collaborate to contribute to the development of the disease. After studying DNA from 29 families, the investigators found that at least one site on chromosome arm 17q interacts with another site on chromosome arm 12q to create a high immunoglobulin E (IgE) phenotype, which is likely associated with asthma.[1]

“Our study is the first to demonstrate a gene-gene interaction in this disease,” said lead author Kathleen C. Barnes, PhD, Assistant Professor of Clinical Immunology at The Johns Hopkins University School of Medicine. The study builds on earlier work by Dr. Barnes and colleagues in which chromosomes 17 and 12 were linked with allergic disease. However, the researchers have yet to find the specific genes on these chromosomes that interact to raise asthma risk.

AN IDEAL POPULATION

Dr. Barnes and colleagues have been studying a number of Afro-Caribbean families in Barbados for several years. This population is ideal for their research because of its homogeneity regarding allergen exposure, diet, living conditions, climate, and genetic makeup. Thus, there are fewer potential study confounders.

Of the 29 families in the most recent study, 25 were extended and four were nuclear. The families had a combined 507 members, 154 of whom had asthma.

To be in the study, subjects with asthma had to meet three inclusion criteria:

• They had to be older than 6 years.

• Their asthma had to be diagnosed by a physician.

• Either both parents had to be available for genotyping or there had to be siblings who would make it possible for the researchers to infer a missing parent’s genotype.

To assess patients for allergic disease, total IgE levels were measured repeatedly in all subjects. A high total IgE value was defined as an age- and gender-adjusted geometric mean level above the sample median of at least 482 ng/mL.

FINDINGS ARE DRIVEN BY ONE FAMILY

The researchers found that one region on 12q and two on 17q appeared to contain genes that collaborate to control the high IgE phenotype. However, the interaction between 17q and 12q occurred primarily in one large extended family with 33 members, 15 of whom had the high IgE phenotype. This finding underscores how difficult it can be to elucidate the genetic complexity of asthma. “You must have just the right genetic and environmental conditions to find linkages to asthma genes,” Dr. Barnes said.

Identifying genetic pathways like the one in this study could eventually lead to new drugs that prevent asthma symptoms by targeting those pathways, Dr. Barnes told RESPIRATORY REVIEWS. A great deal more research is necessary before this can happen, she added, starting with replication of the findings in multiple studies.

—Timothy Begany