Document Detail


Genetic association studies in VLBW infants exemplifying susceptibility to sepsis--recent findings and implications for future research.
MedLine Citation:
PMID:  17429897     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: In recent years, tremendous effort has been carried out to study the genetic basis of susceptibility to development, progression and severity of complex diseases and response to therapy. The ultimate goal of these investigations is to find new tools for prevention and treatment of these complex diseases, such as sepsis in very-low-birth-weight (VLBW) infants. VLBW cohorts have a restricted clinical risk profile for the development of sepsis including immaturity of immune functions and antenatal/perinatal risk factors but also a significant event rate of sepsis within a short period of observational time. Therefore, prospective VLBW cohorts are advantageous for the investigation of candidate genetic risk factors of sepsis compared to adult cohorts. Furthermore, environmental factors are much better documented and highly controlled for VLBW infants in a standardized NICU setting compared to adult cohorts which are influenced by a variety of environmental risk factors, e.g. habits and comorbidities. OBJECTIVE: The aim of this review is to discuss the value and limitations of genetic association studies in VLBW infant cohorts exemplifying recent findings for genetic susceptibility to neonatal sepsis. DATA SOURCE: Published Medline articles reporting on studies of associations between genetic polymorphisms, neonatal sepsis and septic shock in VLBW infants. CONCLUSIONS: Up-to-date, the classical approach to investigate the genetic component of susceptibility to sepsis in VLBW infants by means of twin and concordance studies has not been implemented yet. Regarding the interpretation of data from current genetic association studies, one should be aware of significant differences in cohort size, study design and definition of cases, controls and clinical end points. Furthermore, the contribution of genetic variants to susceptibility to sepsis may be specifically influenced by the immaturity of the immune response in VLBW infants, the selectivity of responsiveness to certain pathogens and the genotopyic/phenotypic variability of pathogens. We provide implications for the conduct and evaluation of future association studies with particular reference to methodological quality standards.
Authors:
Christoph Härtel; Christian Schultz; Egbert Herting; Wolfgang Göpel
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Acta paediatrica (Oslo, Norway : 1992)     Volume:  96     ISSN:  0803-5253     ISO Abbreviation:  Acta Paediatr.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-04-12     Completed Date:  2007-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9205968     Medline TA:  Acta Paediatr     Country:  Norway    
Other Details:
Languages:  eng     Pagination:  158-65     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University of Lübeck Children's Hospital, Ratzeburger Allee 160, 23538 Lübeck, Germany. haertel@paedia.ukl.mu-luebeck.de
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MeSH Terms
Descriptor/Qualifier:
Cytokines / genetics
Genetic Predisposition to Disease
Humans
Infant, Newborn
Infant, Very Low Birth Weight
Receptors, Immunologic / genetics
Sepsis / genetics*,  immunology
Chemical
Reg. No./Substance:
0/Cytokines; 0/Receptors, Immunologic

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