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Am J Respir Crit Care Med. 2008 Jun 1;177(11):1194-200. doi: 10.1164/rccm.200711-1644OC. Epub 2008 Feb 28.

ORMDL3 gene is associated with asthma in three ethnically diverse populations.

Author information

  • 1Lung Biology Center, Department of Medicine, Institute for Human Genetics, University of California, San Francisco, California 94143-2911, USA. joshua.galanter@ucsf.edu

Abstract

RATIONALE:

Independent replication of genetic associations in complex diseases, particularly in whole-genome association studies, is critical to confirm the association.

OBJECTIVES:

A whole-genome association study identified ORMDL3 as a promising candidate gene for asthma in white populations. Here, we attempted to confirm the role of ORMDL3 genetic variants in asthma in three ethnically diverse populations: Mexican, Puerto Rican, and African American.

METHODS:

We used family-based analyses to test for association between seven candidate single-nucleotide polymorphisms (SNPs) in and around the ORMDL3 gene and asthma and related phenotypes in 701 Puerto Rican and Mexican parent-child trios. We also evaluated these seven SNPs and an additional ORMDL3 SNP in 264 African American subjects with asthma and 176 healthy control subjects.

MEASUREMENTS AND MAIN RESULTS:

We found significant associations between two SNPs within ORMDL3 (rs4378650 and rs12603332) and asthma in Mexicans and African Americans (P = 0.028 and 0.001 for rs4378650 and P = 0.021 and 0.001 for rs12603332, respectively), and a trend toward association in Puerto Ricans (P = 0.076 and 0.080 for SNPs rs4378650 and rs12603332, respectively). These associations became stronger among Mexican and Puerto Rican subjects with asthma with IgE levels greater than 100 IU/ml. We did not find any association between ORMDL3 SNPs and baseline lung function or response to the bronchodilator albuterol.

CONCLUSIONS:

Our results confirm that the ORMDL3 locus is a risk factor for asthma in ethnically diverse populations. However, inconsistent SNP-level results suggest that further studies will be needed to determine the mechanism by which ORMDL3 predisposes to asthma.

PMID:
18310477
[PubMed - indexed for MEDLINE]
PMCID:
PMC2408437
Free PMC Article

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