ORMDL3 gene is associated with asthma in three ethnically diverse populations

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • African Americans / genetics*
  • Asthma / ethnology*
  • Asthma / genetics*
  • Case-Control Studies
  • Child
  • Female
  • Forced Expiratory Volume
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mexican Americans / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Puerto Rico / ethnology
  • Spirometry
  • United States / epidemiology

Substances

  • Membrane Proteins
  • ORMDL3 protein, human