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Please use this identifier to cite or link to this item: http://hdl.handle.net/1946/15397

Title: 
  • Genetic Variants in ST2 Previously Associated with Asthma are Associated with Asthma and sST2 Levels in a Brazilian Population Living in an Area Endemic for Schistosoma mansoni
Submitted: 
  • June 2013
Abstract: 
  • Introduction. Asthma is a common, heterogenous syndrome of the respiratory system estimated to affect as many as 300 million people worldwide. A strong overlap between immune response mechanisms responsible for both asthma and resistance to schistosomiasis, a helminth infection, in addition to genetic linkage and association data, supports the hypothesis that genetic determinants conferring resistance to schistosomiasis are also associated with greater risk of asthma. Genome-wide association studies (GWAS) have identified IL1RL1, also known as ST2, as one of the most consistently associated candidate genes for asthma. The aims of this study are to determine whether genetic variants of ST2, previously associated with asthma and serum ST2 levels in asthmatics, are co-associated with resistance to schistosomiasis and serum ST2 levels in participants exposed to schistosomiasis.
    Materials and methods. 697 Brazilian DNA samples stored in -80°C were selected and prepared for genotyping. Four ST2 SNPs associated with asthma and soluble serum ST2 (sST2) levels in an African-American population from Baltimore/Washington were genotyped using TaqMan ABI 7900. Hardy-Weinberg testing and tests for Mendelian inconsistencies were performed using PLINK, and pairwise linkage disequilibrium estimations using Haploview. Tests for genetic association were performed using a generalized estimating equation (GEE) under a dominant model on the soluble adult worm antigen (SWAP)-specific IgE/IgG4 ratio (a measure of resistance to Schistosoma mansoni infection) and sST2 levels. Variables were log-transformed adjusting for age and gender as needed.
    Results. Three ST2 markers (rs1420101, rs12712135 and rs6543119) previously associated with asthma in African Americans are co-associated with changes in sST2 levels in a study population of Brazilians. One marker positively associated with asthma in African-Americans (rs76930359) is negatively associated with wheeze in the study population. The four genetic variants in ST2 are not associated with prevalence or severity of infection by S. mansoni, IgE/IgG4 ratio, nor tIgE levels in this population.
    Conclusion. The coded allele C in the SNP rs76930359 is negatively associated with wheeze and thus could be linked with protection against asthma in this population. The SNPs rs1420101, rs12712135 and rs6543119 are associated with changes in sST2 levels in both Brazilian and African American populations and may be an interesting area of study, for example, in the research on sST2 as a biomarker for disease. Further analyses are needed to better understand the role of variants in ST2 in asthma, expression of sST2, and infection by Schistosoma mansoni.

Description: 
  • Description is in Icelandic Verkefnið var unnið við Læknadeild Johns Hopkins University, Baltimore, Bandaríkjunum
Accepted: 
  • Jun 3, 2013
URI: 
  • http://hdl.handle.net/1946/15397


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