ORMDL3 gene is associated with asthma in three ethnically diverse populations

Joshua Mark Galanter, Shweta Choudhry, Celeste Eng, Sylvette Nazario, José R. Rodríguez-Santana, Jesús Casal, Alfonso Torres-Palacios, Jorge Salas, Rocio Chapela, H. Geoffrey Watson, Kelley Meade, Michael LeNoir, William Rodríguez-Cintrón, Pedro C. Avila, Esteban González Burchard

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1194-1200
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume177
Issue number11
DOIs
StatePublished - Jun 1 2008

Keywords

  • African Americans
  • Asthma
  • Genetics
  • Latinos
  • ORMDL3

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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