title: Suggestive association between variants in IL1RAPL and asthma symptoms in Latin American children.
abstract: Several genome-wide association studies have been conducted to investigate the influence of genetic polymorphisms in the development of allergic diseases, but few of them have included the X chromosome. The aim of present study was to perform an X chromosome-wide association study (X-WAS) for asthma symptoms. The study included 1307 children of which 294 were asthma cases. DNA was genotyped using 2.5 HumanOmni Beadchip from Illumina. Statistical analyses were performed in PLINK 1.9, MACH 1.0 and Minimac2. The variant rs12007907 (g.29483892C>A) in IL1RAPL gene was suggestively associated with asthma symptoms in discovery set (odds ratio (OR)=0.49, 95% confidence interval (CI): 0.37-0.67; P=3.33 × 10-6). This result was replicated in the ProAr cohort in men only (OR=0.45, 95% CI: 0.21-0.95; P=0.038). Furthermore, investigating the functional role of the rs12007907 on the production a Th2-type cytokine, IL-13, we found a negative association between the minor allele A with IL-13 production in the discovery set (P=0.044). Gene-based analysis revealed that NUDT10 was the most consistently associated with asthma symptoms in discovery sample. In conclusion, the rs12007907 variant in IL1RAPL gene was negatively associated with asthma and IL-13 production in our study and a sex-specific association was observed in one of the validation samples. It suggests an effect on asthma susceptibility and may explain differences in severe asthma frequency between women and men.
authors.affiliation: Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Cintia Rodrigues
authors.initials: CR
authors.lastname: Marques
authors.affiliation: Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Gustavo No
authors.initials: GN
authors.lastname: Costa
authors.affiliation: Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil.|Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia, Jequié, Brazil.
authors.forename: Thiago Magalhães
authors.initials: TM
authors.lastname: da Silva
authors.affiliation: Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil.|Centro de Pesquisas Gonçalo Muniz, FIOCRUZ, Salvador, Brazil.
authors.forename: Pablo
authors.initials: P
authors.lastname: Oliveira
authors.affiliation: School of Medicine, ProAR-Center of Excellence in Asthma, Federal University of Bahia School of Medicine, Salvador, Brazil.
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Cruz
authors.affiliation: Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Neuza Maria
authors.initials: NM
authors.lastname: Alcantara-Neves
authors.affiliation: Departamento de Estatística, Instituto de Matemática, Universidade Federal da Bahia, SalvadorBrazil.
authors.forename: Rosemeire L
authors.initials: RL
authors.lastname: Fiaccone
authors.affiliation: Departamento de Medicina Social, Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Brazil.
authors.forename: Bernardo L
authors.identifier: 0000-0001-9843-412X
authors.initials: BL
authors.lastname: Horta
authors.affiliation: Departamento de Medicina Social, Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Brazil.
authors.forename: Fernando Pires
authors.identifier: 0000-0003-3729-0710
authors.initials: FP
authors.lastname: Hartwig
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: Department of Medicine, Hospital Universitario N.S. de Candelaria, Tenerife, Spain.|Department of Medicine, University of California, San Francisco (UCSF), CA, USA.
authors.forename: Maria
authors.identifier: 0000-0003-0332-437X
authors.initials: M
authors.lastname: Pino-Yanes
authors.affiliation: Department of Infectious Disease Epidemiology, Faculty of Epidemiology, London School of Hygiene and Tropical Medicine.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Rodrigues
authors.affiliation: Instituto de Pesquisa Rene Rachou, Fundação Oswaldo Cruz. Av. Augusto de Lima, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Lima-Costa
authors.affiliation: Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mateus H
authors.initials: MH
authors.lastname: Gouveia
authors.affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Hanaisa P
authors.initials: HP
authors.lastname: Sant Anna
authors.affiliation: Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tarazona-Santos
authors.affiliation: Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil.|Centro de Pesquisas Gonçalo Muniz, FIOCRUZ, Salvador, Brazil.
authors.forename: Maurício
authors.initials: M
authors.lastname: Lima Barreto
authors.affiliation: Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.
authors.forename: Camila Alexandrina
authors.initials: CA
authors.lastname: Figueiredo
mesh_terms: D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics*; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D007843:Latin America; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics; D012737:Sex Factors; D000096964:Nudix Hydrolases
chemical_list: D053577:Interleukin-1 Receptor Accessory Protein; D018793:Interleukin-13; D011755:Pyrophosphatases; C407643:IL1RAPL1 protein, human; C469383:NUDT10 protein, human; D000096964:Nudix Hydrolases