title: Polymorphisms in genes involved in folate metabolism as risk factors for oedematous severe childhood malnutrition: a hypothesis-generating study.
abstract: BACKGROUND
  Severe childhood malnutrition (SCM) occurs as both oedematous and non-oedematous syndromes. The reasons why some children develop oedematous SCM (OSCM) have remained elusive but differences in clinical presentation among malnourished children from similar backgrounds suggests that there might be inter-individual variation in susceptibility to OSCM.
  
  
  OBJECTIVE
  To estimate the strength of the association between variants of three genes involved in folate/methyl group metabolism [methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and cystathionine beta-synthase (CBS)] and risk of OSCM.
  
  
  METHODS
  Patients previously admitted to the Tropical Metabolism Research Unit (TMRU) for treatment of either OSCM (cases, n = 74) or non-oedematous SCM (NOSCM, controls, n = 50) were recruited. Genotypes at four sites within the three genes (MTHFR C677T, MTHFR A1298C, MTR A2756G and CBS 844ins68) were determined using PCR-based assays.
  
  
  RESULTS
  The MTHFR 677T [odds ratio (OR) 0.63, 95% CI 0.2-1.7] and MTR 2756G (OR 0.74, 95% CI 0.4-1.4) alleles were associated with moderate reduction in risk of OSCM whereas the CBS 844ins68 allele (OR 1.4, 0.7-2.4) was associated with an increased risk. None of these risks was significant at the 5% level.
  
  
  CONCLUSIONS
  Genetic variation within folate/methyl group metabolic pathways might have a small but potentially important influence on risk of OSCM. Additional, larger data-sets will be required to test the specific hypotheses (about the putative effect size and direction of association) generated in this preliminary study. Such observations have the potential to improve our understanding of the pathogenesis of clinical heterogeneity in severe malnutrition.
authors.affiliation: Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of The West Indies, Mona, Jamaica.
authors.forename: Kwesi G
authors.initials: KG
authors.lastname: Marshall
authors.forename: Sharon
authors.initials: S
authors.lastname: Howell
authors.forename: Asha V
authors.initials: AV
authors.lastname: Badaloo
authors.forename: Marvin
authors.initials: M
authors.lastname: Reid
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: Terrence
authors.initials: T
authors.lastname: Forrester
authors.forename: Colin A
authors.initials: CA
authors.lastname: McKenzie
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D004487:Edema / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D044342:Malnutrition / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003541:Cystathionine beta-Synthase