ADAM33 Is Not Associated with Asthma in Puerto Rican or Mexican Populations

Abstract

A recent study identified the ADAM33 gene as a promising candidate contributing to asthma. In Puerto Rican and Mexican populations, we have genotyped six single nucleotide polymorphisms (SNPs) that were used in the Genetics of Asthma in Latino Americans Study. We chose to study these two populations because in the United States, Puerto Ricans have the highest asthma prevalence, morbidity, and mortality and Mexicans the lowest. We used the transmission disequilibrium test to analyze associations between the ADAM33 gene variants and asthma, asthma severity, bronchodilator responsiveness, and total IgE levels using single SNPs, two to six SNP combinations, and specific haplotypes in 583 trios (proband with asthma and both biological parents). We also genotyped matched control samples to allow case-control analyses. None of the transmission disequilibrium test or case-control results showed significant association in either population. We found no evidence for association of single SNPs with asthma severity, bronchodilator response, or IgE levels in Mexicans or in the combined population. Two SNPs showed a modest association in Puerto Ricans, insignificant when the number of comparisons was taken into account. We conclude that the ADAM33 gene is not an important risk factor for asthma or for asthma-associated phenotypes in Mexicans or in Puerto Ricans.

Association of ADAM33 gene polymorphisms with asthma in Indian children

“…However, in contrast to our study, very large studies conducted by Lind 23 and Raby et al 24 investigating childhood asthma could not find any association between single ADAM33 SNPs or haplotypes and childhood asthma. No association was found between asthma and ADAM33 in Korean, Australian, Chinese, German, Japanese and Caribbean Coast of Colombian populations.…”

“…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.…”

Lack of association between genetic variation in G-protein-coupled receptor for asthma susceptibility and childhood asthma and atopy

“…[1][2][3]5 Of note, other asthma candidate genes identified by positional cloning, such as ADAM33 and SPINK5, also show differences in asthma-associated SNPs among studies. [14][15][16][17] There are several possible explanations for the inconsistency across populations, such as underpowered sample sizes, 18 false positive findings due to ethnic admixture and population stratification, 18 heterogeneity in phenotypes or environmental risk factors 19 and ethnic-specific LD or genetic effect of asthma. 19 There are no known functional SNPs in the GPRA gene, and the role of this gene in asthma is not clear.…”

Genome-wide screen for asthma in Puerto Ricans: evidence for association with 5q23 region

“…All subjects were recruited as part of the Genetics of Asthma in Latino Americans (GALA) study. Recruitment and patient characteristics were described in detail elsewhere (Burchard et al 2004;Choudhry et al 2005;Lind et al 2003) but will be briefly described here. Ethnicity and national origin were self-reported and were ascertained using standardized questions.…”