Association between single nucleotide polymorphisms in TLR4, TLR2, TLR9, VDR, NOS2 and CCL5 genes with acute viral bronchiolitis

作者：Alvarez Alfonso Eduardo^*; Lima Marson Fernando Augusto; Bertuzzo Carmen Silvia; Santiago Bastos Juliana Cristina; Elias Baracat Emilio Carlos; Brandao Marcelo Barciela; Tresoldi Antonia Teresinha; das Neves Romaneli Mariana Tresoldi; Bresciani Almeida Celize Cruz; de Oliveira Therezinha; Schlodtmann Patricia Godano; Correa Ester; Ferreira de Miranda Maria Luisa; dos Reis Marcelo Conrado; De Pieri Jose Vicente; Arns Clarice Weis; Ribeiro Jose Dirceu

来源：Gene, 2018, 645: 7-17.

DOI：10.1016/j.gene.2017.12.022

• Genetics
• Infants
• Respiratory syncytial virus
• Risk factors
• Toll-like receptors

Background: Acute viral bronchiolitis is the leading cause of hospitalization among infants during the first year of life. Most infants hospitalized for bronchiolitis do not present risk factors and are otherwise healthy. Our objective was to determine the genetic features associated with the risk and a severe course of bronchiolitis.
Methods: We prospectively evaluated 181 infants with severe bronchiolitis admitted at three hospitals over a 2 year period, who required oxygen therapy. The control group consisted of 536 healthy adults. Patients were evaluated for the presence of comorbidities (premature birth, chronic respiratory disease, and congenital heart disease), underwent nasopharyngeal aspirate testing for virus detection by multiplex-PCR, and SNPs identification in immune response genes. Patient outcomes were assessed.
Results: We observed association between SNP rs2107538*CCL5 and bronchiolitis caused by respiratory syncytial virus(RSV) and RSV-subtype-A, and between rs1060826*NOS2 and bronchiolitis caused by rhinovirus. SNPs rs4986790*TLR4, rs1898830*TLR2, and rs2228570*VDR were associated with progression to death. SNP rs7656411*TLR2 was associated with length of oxygen use; SNPs rs352162*TLR9, rs187084*TLR9, and rs2280788*CCL5 were associated with requirement for intensive care unit admission; while SNPs rs1927911*TLR4, rs352162*TLR9, and rs2107538*CCL5 were associated with the need for mechanical ventilation.
Conclusions: Our findings provide some evidence that SNPs in CCL5 and NOS2 are associated with presence of bronchiolitis and SNPs in TLR4, TLR2, TLR9, VDR and CCL5 are associated with severity of bronchiolitis.

• 出版日期2018-3-1