Genetic variants associated with severe pneumonia in A/H1N1 influenza infection

• Published in: The European respiratory journal Vol. 39; no. 3; pp. 604 - 610
• Main Authors: Zúñiga, J, Buendía-Roldán, I, Zhao, Y, Jiménez, L, Torres, D, Romo, J, Ramírez, G, Cruz, A, Vargas-Alarcon, G, Sheu, C-C, Chen, F, Su, L, Tager, A M, Pardo, A, Selman, M, Christiani, D C
• Format: Journal Article
• Language: English
• Published: England 01.03.2012
• Subjects: Adult; Antigen-antibody complexes; Carrier Proteins - genetics; Case-Control Studies; Chromosome 1; chromosome 17; chromosome 3; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 17; Complement activation; Fc receptors; Female; Gene polymorphism; Genetic factors; Genetic Predisposition to Disease; Genetic Variation; Genotyping; Humans; Immunity; Immunoglobulin G; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza, Human - genetics; Influenza, Human - immunology; Linkage Disequilibrium; Lung; Male; Mexico; Middle Aged; Mitochondrial Proteins - genetics; Pneumonia; Pneumonia, Viral - genetics; Pneumonia, Viral - immunology; Polymorphism, Single Nucleotide; Receptors, IgG - genetics; Severity of Illness Index; Sex; Single-nucleotide polymorphism; Young Adult; Mexico
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00020611

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.