Variants in the CYSLTR2 are associated with asthma, atopy markers and helminths infections in the Brazilian population

Talita Dos S Jesus; Ryan Dos S Costa; Neuza Maria Alcântara-Neves; Maurício L Barreto; Camila Alexandrina Figueiredo

doi:10.1016/j.plefa.2019.05.003

Variants in the CYSLTR2 are associated with asthma, atopy markers and helminths infections in the Brazilian population

Prostaglandins Leukot Essent Fatty Acids. 2019 Jun:145:15-22. doi: 10.1016/j.plefa.2019.05.003. Epub 2019 May 7.

Authors

Talita Dos S Jesus¹, Ryan Dos S Costa¹, Neuza Maria Alcântara-Neves¹, Maurício L Barreto², Camila Alexandrina Figueiredo³

Affiliations

¹ Departamento de Biorregulação, Laboratório de Imunofarmacologia e Biologia Molecular, Universidade Federal da Bahia, Instituto de Ciências da Saúde, Av. Reitor Miguel Calmon, s/n - Canela, Salvador, Bahia, Brazil.
² Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
³ Departamento de Biorregulação, Laboratório de Imunofarmacologia e Biologia Molecular, Universidade Federal da Bahia, Instituto de Ciências da Saúde, Av. Reitor Miguel Calmon, s/n - Canela, Salvador, Bahia, Brazil. Electronic address: camilavf@ufba.br.

PMID: 31126515
DOI: 10.1016/j.plefa.2019.05.003

Abstract

Background: Asthma is a chronic disease of the airways and its most common phenotype is characterized by a T2 type response with IgE production and inflammatory mediators in response to common allergens. Cysteinyl leukotrienes (CysLTs), LTC4, LTD4 and LTE4, are mediators known to possess important proinflammatory action. CysLTs can bind to the Cysteinyl leukotriene receptor type 2 (CysLTR2) and activate an inflammatory. Polymorphisms in CysLTR2 have been associated with asthma and atopy, although the mechanism is not clear.

Objective: To evaluate the association between genetic polymorphisms in CYSLTR2 with asthma phenotypes, atopy markers and helminth infection.

Methods: Genotyping was performed using a panel Illumina and carried out in 1245 participants of SCAALA program (Social Change, Asthma, Allergy in Latin American). Logistic regressions for asthma, helminth infections (Trichuris trichiura and Ascaris lumbricoides) and allergy markers (skin tests and IgE production) were performed using PLINK 1.9 software adjusted for sex, age, helminth infection and ancestry markers.

Results: The G allele of rs1323556 was negatively associated with asthma in the additive model (OR 0.74, 95% CI 0.59-0.93) and in the dominant model (OR 0.71, 95% CI 0.53-0.74). The G allele of rs1575464 was also negatively associated with asthma in two genetic models, additive (OR 0.77, 95% CI 0.62-0.96) and dominant (OR 0.73, 95% CI 0.55-0.97). The G allele of rs61735175 was positively associated with asthma severity in the additive model (OR 1.72, 95% CI 1.07-2.77) and in the dominant model (OR 1.77, 95% CI 1.09-2.85). Five SNVs were associated with atopy markers and four SNVs were associated with helminth infections.

Conclusion: Polymorphisms in the CYSLTR2 gene are associated with asthma, atopy markers and helminth infection in Brazilian individuals, which may lead to protection or risk for such conditions, however, more studies are needed to evaluate the functional of this variants here in described.

Keywords: Asthma; Atopy; CysLT; CysLTR2; IgE; Polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allergens / genetics
Allergens / immunology
Animals
Asthma / epidemiology
Asthma / genetics*
Asthma / parasitology
Child
Child, Preschool
Female
Genetic Association Studies
Genetic Predisposition to Disease*
Genotype
Helminthiasis / epidemiology
Helminthiasis / genetics
Helminthiasis / parasitology
Helminths / genetics
Helminths / pathogenicity
Humans
Hypersensitivity
Hypersensitivity, Immediate / genetics*
Hypersensitivity, Immediate / parasitology
Inflammation / epidemiology
Inflammation / genetics
Inflammation / parasitology
Male
Phenotype
Polymorphism, Single Nucleotide / genetics
Receptors, Leukotriene / genetics*

Substances

Allergens
Receptors, Leukotriene
cysteinyl leukotriene receptor 2