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Influenza A(H1N1)pdm09: Influence Study of Host Genetic Variants in the Host Sick Individuals by Pandemic Strain in the North and Northeast of Brazil
Alvino Maestri, MD, PhD*, Rita Catarina Medeiros Sousa, MD, PhD1, Mirleirde Cordeiro Dos Santos, Msc2, Wyller Alencar De Mello, PhD2 and Sidney Emanuel Dos Santos, PhD1 (1)Federal University of Pará, Belém, Brazil, (2)Evandro Chagas Institute, Ananindeua, Brazil.
*Presenting Author. Email: [email protected] BACKGROUND Genetic variants of the influenza virus and the host inflammatory response are determinant factors for the development and outcome of infection. The present study investigated genetic variants in seven human genes and their influence on the evolution of infection with Influenza A(H1N1)pdm09.
REFERENCES 1- Neumann G, Noda T, Kawaoka Y (2009) Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459: 931–939. 2- Zhang L et al. (2009) Systems-based candidate genes for human response to influenza infection. Infection, Genetics and Evolution 9: 1148–1157. 3 - Santos NPC et al. (2010) Assessing individual interethnic admixture and population substructure using a 48-insertiondeletion (INSEL) ancestry-informative marker
Presentation Number: 2217
Patients homozygous for the insertion allele of IL4 gene polymorphism exhibited an increased risk of severe disease (OR=2.121, 95% CI=1.21;3.70, p=0.008). The remaining polymorphisms in the CCR5, FCGR2A, HLAG, ILI1A and NFKB1genes were not associated with the severity of this infection. European ancestry was associated with a lower risk of severe disease (OR=0.773, 95% CI=0.639;0.934, p=0.008), while African ancestry was associated with a higher risk of severe disease (OR=1.320, 95% \ CI=1.031;1.689, p=0.028).
METHODS A total of 436 patients with a diagnosis of influenza A(H1N1)pdm09, seen at health services in the northern and northeastern states of Brazil between June 2009 and August 2010, were studied. The subjects were divided into a group that developed mild disease and a group of patients who developed severe disease or died. The genetic variants of the ST3GAL1 (rs113350588 and rs1048479), CCR5 (rs333) and FCGR2A (rs1801274) genes were determined by real-time PCR using Taqman probes. The allelic variants of the HLAG (rs371194629), IL1A (rs3783553), IL4 (rs8179190) and NFKB1(rs28362491) genes were distinguished by multiplex PCR. The proportions of genetic ancestry were determined in all patients using a panel of 48 ancestry informative markers.
RESULTS The rs113350588 and rs1048479 polymorphisms of the ST3GAL1 gene were in linkage disequilibrium in the population studied (D’ = 0.65) and function prediction showed that both variants may alter splicing of the transcript. The GC haplotype was associated with an increased risk of death in subjects with influenza (OR=4.159, 95% CI=1.55;11.12) and the AT haplotype was associated with an increased risk of developing severe disease and death (OR=1.959, 95% CI=1.09;3.52 and OR=2.856, 95% CI=1.41;5.77, respectively).
CONCLUSION The present research demonstrates for the first time the influence of genetic ancestry and of genetic variants in the ST3GAL1 and IL4 genes on the severity and outcome of infection with Influenza A(H1N1)pdm09.