ORMDL3 gene is associated with asthma in three ethnically diverse populations.
BACKGROUND
Independent replication of genetic associations in complex diseases, particularly in whole-genome association studies, is critical to confirm the association.


OBJECTIVE
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.


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.
Galanter
Joshua
J
Lung Biology Center, Department of Medicine, Institute for Human Genetics, University of California, San Francisco, California 94143-2911, USA. joshua.galanter@ucsf.edu
Choudhry
Shweta
S
Eng
Celeste
C
Nazario
Sylvette
S
Rodríguez-Santana
José R
JR
Casal
Jesús
J
Torres-Palacios
Alfonso
A
Salas
Jorge
J
Chapela
Rocio
R
Watson
H Geoffrey
HG
Meade
Kelley
K
LeNoir
Michael
M
Rodríguez-Cintrón
William
W
Avila
Pedro C
PC
Burchard
Esteban González
EG
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001249:Asthma / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011647:Puerto Rico / Q000208:ethnology; D013147:Spirometry; D014481:United States / Q000453:epidemiology
D008565:Membrane Proteins; C464399:ORMDL3 protein, human