IL8 Polymorphisms associated with earlier and increased incidence of ALRI in children from PAPUA new Guinea (PNG)

Abstract

Children from the highlands of PNG have amongst the highest rates of ALRI morbidity and mortality in the world. Aim To test the hypothesis that interleukin (IL) 8 genotypes associated with altered IL8 expression levels and thus neutrophil recruitment would be involved in the development of ALRIs from birth to 18 months of age. Methods Infants (n = 319) were recruited at birth and had comprehensive ALRI surveillance to 18 months of age. Severity was determined using WHO criteria. Microbiology identified a large variety of bacterial serotypes (particularly Streptococcus pneumoniae and Haemophilus influenzae) and respiratory viruses in routine and sick nasal swabs. DNA was extracted from blood for 281 children and IL8 T-251A (rs4073) & C781T (rs2227306) genotyped using Sequenom MassARRAY. SPSS Kaplan-Meier survival curves and multiple regression models (adjusted for gender and follow-up time) analysed data. Results Children were 52% male and 57.7% had a moderate/severe ALRI. Children with IL8 781 CT or CC had 2.85 months (p = 0.04) earlier mean age of first moderate/severe ALRI compared to children with 781 TT. The IL8 -251 genotypes were associated with total number of ALRIs (p = 0.04). Children with -251 AA had fewer ALRI in their first 18 months than -251 TT (Geometric mean = 1.6 vs. 2.0, respectively, adjusted for gender). In summary, the opposite genotypes to those previously associated with RSV bronchiolitis are associated with ALRI in children from PNG. Conclusion Alternate IL8 genotypes may precipitate and exacerbate childhood ALRI caused by both bacterial and viral pathogens than RSV alone.