Single nucleotide polymorphisms in genes of circulatory homeostasis in surviving pediatric intensive care patients with meningococcal infection.
OBJECTIVE
In the course of a meningococcal infection, invasive and severe disease occurs in a restricted number of individuals. The predominant mechanism of death in case of meningococcal septic shock is circulatory failure. Inotropic requirements between patients vary widely. We investigated whether polymorphisms in genes regulating the hemodynamic response influence the amount of inotropics required or the susceptibility to severe meningococcal disease.


METHODS
Retrospective case control study.


METHODS
Single-center pediatric intensive care unit (PICU).


METHODS
Fifty-six cases (all consecutive patients admitted to the PICU between 1993 and 2001 with a proven meningococcal infection) and 136 controls. Patients were divided into two groups according to their inotropic requirements.


METHODS
DNA analysis was performed to determine the polymorphisms of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, alpha-adducin, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 genes.


RESULTS
For the alpha-adducin gene a significant difference of the genotype distribution was found between the cases and controls. The odds ratio for admission to the PICU with meningococcal sepsis with or without meningitis, for carriers of the variant allele (Gly460Trp or Trp460Trp) was 2.1 (95% confidence interval 1.11-4.04; p < 0.02). Cases, homozygote for the wild-type allele of the beta-1 adrenergic receptor at locus 389, were more likely to have a low pediatric risk of mortality score on admission (odds ratio 3.6, 95% confidence interval 1.11-11.76). No difference was found in the distribution of the beta-adrenergic receptor gene-1, beta-adrenergic receptor gene-2, angiotensin converting enzyme, and angiotensin II type-1 receptor-1 polymorphisms between the two groups of patients or between cases and controls.


CONCLUSIONS
Among patients admitted to the PICU with a meningococcal infection, the variant allele of the alpha-adducin gene was more prevalent compared with controls. Patients with the variant allele of the beta-adrenergic receptor gene-1 at locus 389 were more likely to have a high pediatric risk of mortality score on admission. The mechanism and clinical relevance of these findings is unclear.
Bunker-Wiersma
Heleen E
HE
Pediatric Intensive Care Unit, The Emma Children's hospital/Academic Medical Center, Amsterdam, Netherlands. h.e.wiersma@amc.uva.nl
Koopmans
Richard P
RP
Kuipers
Taco W
TW
Knoester
Hennie
H
Bos
Albert P
AP
D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D008589:Meningococcal Infections / Q000150:complications / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D012189:Retrospective Studies; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D018342:Receptors, Adrenergic, beta-1; D000099291:Adducins