A pilot study of host genetic variants associated with influenza-associated deaths among children and young adults

Abstract

We compared the prevalence of 8 polymorphisms in the tumor necrosis factor and mannose-binding lectin genes among 105 children and young adults with fatal influenza with US population estimates and determined in subanalyses whether these polymorphisms were associated with sudden death and bacterial co-infection among persons with fatal influenza. No differences were observed in genotype prevalence or minor allele frequencies between persons with fatal influenza and the reference sample. Fatal cases with low-producing MBL2 genotypes had a 7-fold increased risk for invasive methicillin-resistant Staphylococcus aureus (MRSA) co-infection compared with fatal cases with high- and intermediate-producing MBL2 genotypes (odds ratio 7.1, 95% confidence interval 1.6-32.1). Limited analysis of 2 genes important to the innate immune response found no association between genetic variants and fatal influenza infection. Among children and young adults who died of influenza, low-producing MBL2 genotypes may have increased risk for MRSA co-infection.

Figure 1

Variant frequency and 95% confidence intervals for fatal influenza cases compared with the NHANES reference group for 8 single-nucleotide polymorphisms. Allele frequency did not differ significantly between cases and the reference group for any single-nucleotide polymorphism. NHANES, National Health and Nutrition Examination Survey. Error bars represent confidence intervals.

Figure 2

Frequency and 95% confidence intervals for fatal influenza cases (n = 105) compared with the NHANES reference group for pooled structural genotypes (AA/AO/OO) of MBL2 and categorization of MBL production on the basis of genotype (low/intermediate/high). Frequencies did not differ significantly between cases and the reference group. MBL, mannose-binding lectin; NHANES, National Health and Nutrition Examination Survey; MBL2, mannose-binding lectin gene. Error bars represent confidence intervals.