A Six-SNP Haplotype of <i>ADAM33 </i>Is Associated with Asthma in a Population of Cartagena, Colombia

Abstract

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.

Association of a Disintegrin and Metalloprotease 33 Gene Polymorphisms and Their Haplotypes With Asthma in the North‑indian Population

“…Same contradictory results were observed for SNPs T1 and T2 from another study done by Vergara et al, [16] on the population of Cartagena, Colombia, and in this study six SNPs were analyzed including T1 and T2. A study on the South-Indian population by Bijanzadeh et al, [14] in children as well as on adults, also failed to find an association between asthma and the T1 SNP of ADAM33.…”

“…However, further studies are needed to confirm the mechanistic and pathophysiological role of ADAM33 SNPs in asthma susceptibility. [14] South India (Mysore) (cc) 100/50 − * * * * * Vergara et al, 2010 [16] …”

“…[7] A number of studies have been published with very diverse results, suggesting its role in asthma. [7,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] However, results were not similar in all the studied populations, as some studies showed a positive association of ADAM33 polymorphisms with asthma and another different set of studied populations were not associated with asthma. There is a need to study all of the most common single nucleotide polymorphisms (SNPs) association with asthma together with gene-environment and clinical factors worldwide to find out which are universally associated with asthma.…”

Association of ADAM33 gene polymorphisms with asthma in Indian children

“…No association was found between asthma and ADAM33 in Korean, Australian, Chinese, German, Japanese and Caribbean Coast of Colombian populations. 21,25,[27][28][29]31 A recent report by Bijanzadeh and colleagues also failed to find an association between asthma and the T1 SNP of the ADAM33 gene in a South Indian population. 34 This may be because of allelic heterogeneity, a single disorder caused by different mutations within a gene.…”

“…Associations between distinct single-nucleotide polymorphisms (SNPs) of ADAM33 and various subphenotypes of asthma as well as bronchial hyperresponsiveness have been reported. 7,14,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Several SNPs in ADAM33 have been shown to be significantly associated with asthma, suggesting an important role for ADAM33 in the etiology of asthma. 7,14,19,20,32 However, most data available for ADAM33 and asthma have been obtained from Caucasians, but little data on ADAM33 SNPs associated with asthma and atopic disease are available for Asian populations.…”