Nitric oxide synthase 2A (NOS2A) polymorphisms are not associated with invasive pneumococcal disease.
BACKGROUND
Streptococcus pneumoniae (pneumococcus) is responsible for over one million deaths per year, with young children, the elderly and immunocompromised individuals being most at risk. Approximately half of East African children have been reported to be asymptomatic carriers of pneumococcus with invasive infection occurring after the disruption of the respiratory membrane which is believed to be caused by the host immune response. Racial incidence of invasive pneumococcal disease (IPD) is higher in certain populations even after adjusting for environmental factors suggesting a genetic component to disease susceptibility. The nitric oxide synthase 2A (NOS2A) gene is responsible for the production of nitric oxide under pathological conditions including host defence against bacterial infection. Nitric oxide is a modulator of apoptotic and inflammatory cascades and endothelial permeability. We hypothesised that genetic variants within this gene may predispose to disease risk and survival.


METHODS
A cohort of 299 children with IPD (221 meningitis, 41 pneumonia and 37 with bacteraemia) and 931 age matched controls from Malawi were used in this study. We investigated nine haplotype tagging single nucleotide polymorphisms within the NOS2A gene and compared the presence or absence of the minor alleles in cases and controls and survivors and non-survivors within the cases.


RESULTS
We observed no significant associations between cases and controls or with survival in either all IPD cases or in the separate analysis of meningitis cases. A near significant association was obtained for the comparison of rs8078340 in cases and controls (p-value, 0.078). However, results were unadjusted for multiple testing.


CONCLUSIONS
Our results suggest that polymorphic variation within the NOS2A gene does not influence invasive pneumococcal disease susceptibility or survival.
Payton
Antony
A
Centre for Integrated Genomic Medical Research, Stopford Building, The University of Manchester, Manchester, UK. Tony.Payton@man.ac.uk
Payne
Debbie
D
Mankhambo
Limangeni A
LA
Banda
Daniel L
DL
Hart
C Anthony
CA
Ollier
William Er
WE
Carrol
Enitan D
ED
D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D008295:Malawi; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011008:Pneumococcal Infections / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide
C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II