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Gene. 2019 Oct 5;715:143991. doi: 10.1016/j.gene.2019.143991. Epub 2019 Jul 26.

Genetic variants in 17q12-21 locus and childhood asthma in Brazil: Interaction with Varicella zoster virus seropositivity.

Author information

1
Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil; Departamento de Ciências da Saúde, Universidade Salvador (UNIFACS), Brazil. Electronic address: gustavokosta@gmail.com.
2
Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
3
Instituto de Matemática, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
4
Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil.
5
Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
6
Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil; Instituto de Matemática, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
7
Department of Epidemiology and Populations Health, London School of Hygiene and Tropical Medicine, UK.
8
Center of Data and Knowledge Integration for Health, Instituto Gonçalo Muniz, Fundação Osvaldo Cruz, Salvador, Brazil; Fundação Osvaldo Cruz, Salvador, Brazil.

Abstract

BACKGROUND:

Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations.

OBJECTIVE:

This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children.

METHODS:

This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS).

RESULTS:

Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44-3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus.

CONCLUSIONS:

We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus.

KEYWORDS:

17q12-21; Atopy; Childhood asthma; Varicella zoster

PMID:
31357023
DOI:
10.1016/j.gene.2019.143991
[Indexed for MEDLINE]

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