Article
Suggestive association between variants in IL1RAPL and asthma symptoms in Latin American children
Registro en:
MARQUES, C. R. et al. Suggestive association between variants in IL1RAPL and asthma symptoms in Latin American children. European Journal of Human Genetics, v. 25, p. 439–445, 2017.
1018-4813
10.1038/ejhg.2016.197
Autor
Marques, Cintia Rodrigues
Costa, Gustavo No
Silva, Thiago Magalhães da
Oliveira, Pablo Rafael Silveira
Cruz Filho, Alvaro Augusto Souza da
Neves, Neuza Maria Alcantara
Fiaccone, Rosemeire Leovigildo
Horta, Bernardo Lessa
Hartwig, Fernando Pires
Burchard, Esteban G
Pino-Yanes, Maria
Rodrigues, Laura C
Costa, Maria Fernanda Furtado de Lima e
Pereira, Alexandre C
Gouveia, Mateus Henrique
Sant Anna, Hanaisa de Pla e
Santos, Eduardo Martin Tarazona
Barreto, Maurício Lima
Figueiredo, Camila Alexandrina Viana de
Resumen
Oliveira, Pablo Rafael Silveira; Barreto, Maurício Lima. Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil. 1Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil; 2Instituto de Saúde Coletiva, Universidade Federal da Bahia, Salvador, Brazil; 3Departamento de
Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia, Jequié, Brazil; 4Centro de Pesquisas Gonçalo Muniz, FIOCRUZ, Salvador, Brazil; 5School of Medicine, ProARCenter
of Excellence in Asthma, Federal University of Bahia School of Medicine, Salvador, Brazil; 6Departamento de Estatística, Instituto de Matemática, Universidade Federal da
Bahia, Salvador, Brazil; 7Departamento de Medicina Social, Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Brazil; 8Department of
Medicine, University of California, San Francisco, CA, USA; 9Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA;
10Department of Medicine, Hospital Universitario N.S. de Candelaria, Tenerife, Spain; 11Department of Medicine, University of California, San Francisco (UCSF), CA, USA;
12Department of Infectious Disease Epidemiology, Faculty of Epidemiology, London School of Hygiene and Tropical Medicine; 13Instituto de Pesquisa Rene Rachou, Fundação
Oswaldo Cruz. Av. Augusto de Lima, Belo Horizonte, Minas Gerais, Brazil; 14Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, Brazil;
15Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Department of Science and Technology (DECIT, Ministry of Health) and National Fund for Scientific and
Technological Development (FNDCT, Ministry of Science and Technology), Funding of Studies and Projects (FINEP, Ministry of Science and Technology, Brazil) 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.