A Six-SNP haplotype of ADAM33 is associated with asthma in a population of Cartagena, Colombia.
BACKGROUND
A disintegrin and metalloprotein-33 (ADAM33) participates in the bronchial remodeling process in asthma, and genetic analyses pointed it out as a candidate gene in asthma.


METHODS
To analyze the association between ADAM33 and asthma and total and mite-specific IgE levels in a population of the Caribbean Coast of Colombia, we genotyped 6 single-nucleotide polymorphisms of ADAM33 in 429 asthmatics, 401 controls and 116 family trios using fluorogenic probes. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Case-control and family-based analyses were performed. Case-control association analyses were corrected by population stratification using a set of 52 ancestry-informative markers.


RESULTS
Eight common haplotypes were identified; among them, H4 (GCAGGG) was associated with asthma in the family group (Z score: -2.049, p = 0.04). We also found an association between the TT genotype of ST+7 and asthma in the case-control study (p = 0.05) that disappeared after correcting for multiple testing. In the family-based analysis, this genotype was a risk factor for asthma (p = 0.01), high total IgE (Z score: 2.546, p = 0.01) and high specific IgE against B. tropicalis (p = 0.02) and D. pteronyssinus (Z score: 2.414, p = 0.01). V4 was associated with specific IgE against B. tropicalis (p = 0.03); T2 with asthma (p = 0.03), high total IgE (p = 0.02) and IgE against D. pteronyssinus (p = 0.03) and T1 with high total IgE (p = 0.04). None of these associations was maintained after correction for multiple testing.


CONCLUSIONS
Our findings suggest a relevant role of ADAM33 in thepathogenesis of asthma in this population.
Vergara
Candelaria I
CI
Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.
Acevedo
Nathalie
N
Jiménez
Silvia
S
Martínez
Beatriz
B
Mercado
Dilia
D
Gusmão
Leonor
L
Barnes
Kathleen C
KC
Caraballo
Luis
L
D051722:ADAM Proteins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D003105:Colombia / Q000453:epidemiology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D008925:Mites / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D000485:Allergens; D007073:Immunoglobulin E; D051722:ADAM Proteins; C450441:ADAM33 protein, human