title: Siaα2-3Galβ1- Receptor Genetic Variants Are Associated with Influenza A(H1N1)pdm09 Severity.
abstract: Different host genetic variants may be related to the virulence and transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as binding of the virus to the entry receptor on the cell of infected individuals and the host immune response. In the present study, two genetic variants of the ST3GAL1 gene, which encodes the Siaα2-3Galβ1- receptor to which influenza A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of the study, the rs113350588 and rs1048479 polymorphisms identified in this sample were genotyped in a sample of 356 subjects from the northern and northeastern regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of the polymorphisms was performed in silico and the influence of these variants on the severity of infection was evaluated. The results suggest that rs113350588 and rs1048479 may alter the function of ST3GAL1 either directly through splicing regulation alteration and/or indirectly through LD with SNP with regulatory function. In the study the rs113350588 and rs1048479 polymorphisms were in linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype was associated with an increased risk of death in subjects with influenza (OR = 4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476, 95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the association of ST3GAL1 gene haplotypes on the risk of more severe disease and death in patients infected with Influenza A(H1N1)pdm09 virus.
authors.affiliation: Laboratory of Human and Medical Genetics, Federal University of Pará, Belém, Pará, Brazil.
authors.forename: Alvino
authors.initials: A
authors.lastname: Maestri
authors.affiliation: Center of Cancer Studies, Federal University of Pará, Belém, Pará, Brazil.
authors.forename: Vinicius Albuquerque
authors.initials: VA
authors.lastname: Sortica
authors.affiliation: Centre of Epidemiological research, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Tovo-Rodrigues
authors.affiliation: Laboratory of Respiratory Viruses, Virology Section, Evandro Chagas Institute, Ananindeua, Pará, Brazil.
authors.forename: Mirleide Cordeiro
authors.initials: MC
authors.lastname: Santos
authors.affiliation: Laboratory of Respiratory Viruses, Virology Section, Evandro Chagas Institute, Ananindeua, Pará, Brazil.
authors.forename: Luana
authors.initials: L
authors.lastname: Barbagelata
authors.affiliation: Laboratory of Human and Medical Genetics, Federal University of Pará, Belém, Pará, Brazil.
authors.forename: Milene Raiol
authors.initials: MR
authors.lastname: Moraes
authors.affiliation: Laboratory of Respiratory Viruses, Virology Section, Evandro Chagas Institute, Ananindeua, Pará, Brazil.
authors.forename: Wyller
authors.initials: W
authors.lastname: Alencar de Mello
authors.affiliation: Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Leonor
authors.initials: L
authors.lastname: Gusmão
authors.affiliation: Laboratory of Respiratory Viruses, Virology Section, Evandro Chagas Institute, Ananindeua, Pará, Brazil; Tropical Medicine Institute, Federal University of Pará, Belém, Pará, Brazil.
authors.forename: Rita Catarina Medeiros
authors.initials: RC
authors.lastname: Sousa
authors.affiliation: Laboratory of Human and Medical Genetics, Federal University of Pará, Belém, Pará, Brazil.
authors.forename: Sidney
authors.initials: S
authors.lastname: Emanuel Batista Dos Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000150:complications / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics; D012306:Risk; D045169:Severe Acute Respiratory Syndrome / Q000209:etiology / Q000401:mortality; D012720:Severity of Illness Index; D012799:Sialyltransferases / Q000235:genetics*; D055815:Young Adult; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
chemical_list: D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase