AUTHOR=Pavón-Romero Gandhi F. , Pérez-Rubio Gloria , Ramírez-Jiménez Fernando , Ambrocio-Ortiz Enrique , Bañuelos-Ortiz Elisé , Alvarado-Franco Norma , Xochipa-Ruiz Karen E. , Hernández-Juárez Elizabeth , Flores-García Beatriz A. , Camarena Ángel E. , Terán Luis M. , Falfán-Valencia Ramcés 

TITLE=MS4A2-rs573790 Is Associated With Aspirin-Exacerbated Respiratory Disease: Replicative Study Using a Candidate Gene Strategy

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00363

DOI=10.3389/fgene.2018.00363

ISSN=1664-8021

ABSTRACT=<p>Aspirin exacerbated respiratory disease (AERD) is a set of diseases of the unified airway, and its physiopathology is related to disruption of the metabolism of arachidonic acid (AA). Genetic association studies in AERD had explored single nucleotide polymorphism (SNPs) in several genes related to many mechanisms (AA metabolism, inflammation, drug metabolism, etc.) but most lack validation stages in second populations. Our aim is to evaluated whether contribution to susceptibility of SNPs reported in other populations are associated with AERD in Mexican Mestizo patients. We developed a replicative study in two stages. In the first, 381 SNPs selected by fine mapping of associated genes, (previously reported in the literature), were integrated into a microarray and tested in three groups (AERD, asthma and healthy controls -HC-) using the GoldenGate array. Results associated to risk based on genetic models [comparing: AERD vs. HC (comparison 1, C1), AERD vs. asthma (C2), and asthma vs. HC (C3)] were validated in the second stage in other population groups using qPCR. In the first stage, we identified 11 SNPs associated with risk in C1.The top SNPs were <italic>ACE-</italic>rs4309C (<italic>p</italic> = 0.0001) and <italic>MS4A2-</italic>rs573790C (<italic>p</italic> = 0.0002). In C2, we detected 14 SNPs, including <italic>ACE-</italic>rs4309C (<italic>p</italic> = 0.0001). In C3, we found <italic>MS4A2-</italic>rs573790C (<italic>p</italic> = 0.001). Using genetic models, C1 <italic>MS4A2-</italic>rs57370 CC (<italic>p</italic> = 0.001), and <italic>ACE-</italic>rs4309 CC (<italic>p</italic> = 0.002) had associations. In C2 <italic>ACE-</italic>rs4309 CC (<italic>p</italic> = 0.0001) and C3 <italic>MS4A2-</italic>rs573790 CC (<italic>p</italic> = 0.001) were also associate with risk. In the second stage, only <italic>MS4A2-</italic>rs573790 CC had significance in C1 and C3 (<italic>p</italic> = 0.008 and <italic>p</italic> = 0.03). We concluded that rs573790 in the <italic>MS4A2</italic> gene is the only SNP that supports an association with AERD in Mexican Mestizo patients in both stages of the study.</p>