title: Genetic variants associated with severe pneumonia in A/H1N1 influenza infection.
abstract: The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility. We carried out a case-control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA). Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69-4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64-4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63-4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89-5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium. These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A, C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity.
authors: Instituto Nacional deEnfermedades Respiratorias IsmaelCosio Villegas, Universidad Nacional Autónoma de México, México City, Mexico.
authors: J
authors: J
authors: Zúñiga
authors: I
authors: I
authors: Buendía-Roldán
authors: Y
authors: Y
authors: Zhao
authors: L
authors: L
authors: Jiménez
authors: D
authors: D
authors: Torres
authors: J
authors: J
authors: Romo
authors: G
authors: G
authors: Ramírez
authors: A
authors: A
authors: Cruz
authors: G
authors: G
authors: Vargas-Alarcon
authors: C-C
authors: CC
authors: Sheu
authors: F
authors: F
authors: Chen
authors: L
authors: L
authors: Su
authors: A M
authors: AM
authors: Tager
authors: A
authors: A
authors: Pardo
authors: M
authors: M
authors: Selman
authors: D C
authors: DC
authors: Christiani
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000235:genetics* / Q000276:immunology; D015810:Linkage Disequilibrium; D008297:Male; D008800:Mexico; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D011024:Pneumonia, Viral / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; C445323:FCGR2A protein, human; D024101:Mitochondrial Proteins; D017452:Receptors, IgG