Genetic polymorphisms in collectins and Toll-like receptor 4 as factors influencing susceptibility to severe RSV infections and otitis media
1University of Oulu, Faculty of Medicine, Institute of Clinical Medicine, Department of Paediatrics
2University of Oulu, Biocenter Oulu
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|Persistent link:|| http://urn.fi/urn:isbn:9789514290671
|Publish Date:|| 2009-03-24
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic dissertation to be presented with the assent of the Faculty of Medicine of the University of Oulu for public defence in Auditorium 12 of Oulu University Hospital, on 3 April 2009, at 12 noon
Docent Ville Peltola
Docent Harri Saxén
Respiratory syncytial virus (RSV) is one of the most common pathogens for early childhood respiratory tract infections. Most children are infected by RSV, approximately 1% of infants require hospital care. RSV infections are often accompanied by otitis media (OM). Surfactant proteins A and D (SP-A and SP-D) are involved in lung function and innate immunity. The proteins are capable of recognizing surface patterns in pathogens and function as a defense before the acquired immunity is developed. The Toll-like receptor (TLR) family is associated to several pathogens. The role of the TLR-family is to recognize pathogens and activate the immune defense.
The aim of the thesis was to investigate the genetic association of RSV and OM infections in infants. A candidate gene approach was used study SP-A, SP-D and TLR4 in severe RSV bronchiolitis. Association between SP-A and OM was also studied. A case-control study setup was used for all studies. 1700 samples were collected for the studies.
The results revealed genetic association between SP-A gene variation and severe RSV infections. SP-A allele 1A3 was overrepresented in RSV infants, the allele 1A was present more often in the control population. SP-D allele Met11 and genotype Met/Met were predisposing to severe RSV infections. The TLR4 gene did not show direct association with severe RSV. However, we showed for the first time difference in association in two separate epidemics. In the OM study, an association was shown between SP-A gene variations and otitis media in children.
The present results have brought new information about innate defense and the genetic variations and associations involved. The results will help understand the mechanisms of innate defense and predisposition to infections. The results also present possibilities to investigate and develop new treatment strategies.
Acta Universitatis Ouluensis. D, Medica
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