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. 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

Joshua Galanter  1 , 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
Affiliations

ORMDL3 gene is associated with asthma in three ethnically diverse populations

Joshua Galanter et al. Am J Respir Crit Care Med. .

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.

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Figures

<b>Figure 1.</b>
Figure 1.
Schematic of the location of the ORMDL3 gene on chromosome 17, and the position of the eight genotyped single-nucleotide polymorphisms (SNPs) in relation to the gene.
<b>Figure 2.</b>
Figure 2.
Plot of odds ratio of association analysis of ORMDL3 single-nucleotide polymorphisms (SNPs) and haplotypes with asthma in African Americans (solid bars), Mexicans (light shaded bars), and Puerto Ricans (dark shaded bars). Error bars indicate 95% confidence intervals.
See this image and copyright information in PMC

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