Association of G-protein-coupled receptor 154 with asthma and total IgE in a population of the Caribbean coast of Colombia

Authors

  • C. Vergara,

    1. Institute for Immunological Research, University of Cartagena, Cartagena, Colombia,
    2. Fundemeb. Foundation for the Development of Medical and Biological Sciences, Cartagena, Colombia,
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  • S. Jiménez,

    1. Institute for Immunological Research, University of Cartagena, Cartagena, Colombia,
    2. Fundemeb. Foundation for the Development of Medical and Biological Sciences, Cartagena, Colombia,
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  • N. Acevedo,

    1. Institute for Immunological Research, University of Cartagena, Cartagena, Colombia,
    2. Fundemeb. Foundation for the Development of Medical and Biological Sciences, Cartagena, Colombia,
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  • B. Martínez,

    1. Institute for Immunological Research, University of Cartagena, Cartagena, Colombia,
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  • D. Mercado,

    1. Institute for Immunological Research, University of Cartagena, Cartagena, Colombia,
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  • L. Gusmão,

    1. IPATIMUP. Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal and
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  • N. Rafaels,

    1. Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University (JHU), Baltimore, MD 21224, USA
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  • T. Hand,

    1. Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University (JHU), Baltimore, MD 21224, USA
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  • K. C. Barnes,

    1. Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University (JHU), Baltimore, MD 21224, USA
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  • L. Caraballo

    1. Institute for Immunological Research, University of Cartagena, Cartagena, Colombia,
    2. Fundemeb. Foundation for the Development of Medical and Biological Sciences, Cartagena, Colombia,
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Correspondence:
Luis Caraballo, Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.
E-mail: luiscaraballo@telecom.com.co

Summary

Background G protein-coupled receptor 154 was described as an asthma susceptibility gene by positional cloning. It has been subsequently associated with asthma and other inflammatory diseases in several populations with different ethnic origin. Replication of associations adds reliability to these findings.

Objective To analyze the association of G protein-coupled receptor 154 with asthma and total and mite-specific IgE levels in a population of the Caribbean Coast of Colombia.

Methods We genotyped seven single nucleotide proteins (SNPs) in GPR154 in 475 asthmatics, 394 controls and 116 families from Cartagena, Colombia using either SnaPshot or TaqMan. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Hardy–Weinberg equilibrium was assessed and case–control and family-based analyses were performed to evaluate the association between the SNPs and their haplotypes and asthma and IgE. Association analyses in the case–control dataset were corrected by population stratification using 52 ancestry informative markers.

Results Allelic distribution was similar to that described in other populations. Two SNPs were associated with the same direction of the effect in both datasets. Allele A of Hopo546333 was protective for asthma (case–control OR: 0.42; 95% CI: 0.17–0.99, P=0.042; P=0.043; families Z score=−2,236; P=0.025). Similarly, allele C of rs740347 conferred low risk for asthma (OR: 0.44; 95% CI: 0.28–0.70, P=0.00017; Pc=0.00037) and total IgE (OR: 0.29; 95% CI: 0.09–0.88, P=0.015; Pc=0.030) in the case–control study and families (Z score=−3.207, P=0.0013; Z score=−3.182, P=0.0014, respectively). Haplotype CCAGGT was associated with total IgE (OR: 1.76; 95% CI: 1.14–2.71, P=0.006, Pc=0.007) in the case–controls group and CGCGGT with both phenotypes (P=0.044 and P=0.032, respectively) in families. Neither SNPs nor haplotypes were associated with levels of mite-specific IgE.

Conclusions Our findings in a sample of asthmatics from Colombia suggest a relevant role of G protein-coupled receptor 154 in the pathogenesis of asthma and allergy.

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