A preliminary examination of the effects of genetic variants of redox enzymes on susceptibility to oedematous malnutrition and on percentage cytotoxicity in response to oxidative stress in vitro.
BACKGROUND
The causes of oedematous vs non-oedematous childhood malnutrition (OM vs NOM) remain elusive. It is possible that inherited differences in handling oxidant stressors are a contributing factor.


OBJECTIVE
To test for associations between polymorphisms in five genes and (i) risk of OM, a case-control study, and (ii) percentage cytotoxicity in peripheral blood mononuclear cells (PBMCs) exposed to hydrogen peroxide (H(2)O(2)), an in vitro cell challenge study.


METHODS
Participants had been admitted previously for treatment of OM (cases, n = 74) or NOM (controls, n = 50), or were an independent set of healthy pregnant women (n = 47) who donated peripheral blood mononuclear cells. We tested for associations between genetic variation and outcome using single markers or a bivariate score constructed by counting numbers of deleterious alleles for each of 15 possible pairs of markers.


RESULTS
In the case-control study there were no significant single-marker associations with OM. We did find that higher bivariate scores were associated with OM for the pair of NAD(P)H:quinone oxidoreductase 1 and catalase (odds ratio 2·00, 95% CI 1·05-3·82). In the cell challenge experiments, there were no significant associations with percentage cytotoxicity.


CONCLUSIONS
Variation in this small set of genes seems unlikely to have a large impact on either risk of OM or cytotoxicity after H(2)O(2) exposure. The use of larger sample sizes to test the effects of a much larger set of genetic variants will be required in order to determine whether genetic variation contributes to the risk of OM. Such studies have potential for improving our understanding of causal pathways in OM.
Tropical Metabolism Research Unit, University of the West Indies, Mona, Jamaica.
K G
KG
Marshall
K
K
Swaby
K
K
Hamilton
S
S
Howell
R C
RC
Landis
I R
IR
Hambleton
M
M
Reid
H
H
Fletcher
T
T
Forrester
C A
CA
McKenzie
D016022:Case-Control Studies; D002648:Child; D015362:Child Nutrition Disorders / Q000201:enzymology* / Q000235:genetics*; D002675:Child, Preschool; D004487:Edema / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000378:metabolism; D018384:Oxidative Stress; D011247:Pregnancy