title: Possible selection of host folate pathway gene polymorphisms in patients with malaria from a malaria endemic region in North East India.
abstract: Recent studies in experimental mice have shown that mild deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme confers protection against malaria, thus providing an important basis for the hypothesis that MTHFR polymorphism, i.e. C677T, might have been subjected to selection pressure against malaria. The present study was undertaken in a malaria endemic region in North East India to assess whether a similar selection advantage exists for other genes in folate metabolism pathway.
  
  
  
  A total of 401 subjects including 131 symptomatic malaria, 97 asymptomatic malaria and 173 normal healthy controls were analysed for nine polymorphisms (single-nucleotide polymorphisms [SNPs] in eight genes and insertion/deletion in one gene): MTHFR C677T, methionine synthase reductase (MTRR) A66G, glutamate carboxypeptidase II (GCPII) C1561T, cystathionine beta-synthase (CBS) 844ins68, reduced folate carrier-1 (RFC-1) G80A, serine hydroxymethyltransferase (SHMT) C1420T, methionine synthase (MTR) A2756G, MTHFR G1793A (D 919G), glycine N-methyltransferase (GNMT) 1289 by PCR-RFLP technique. Differences in frequencies of genotype distribution of each polymorphic marker between these groups were evaluated.
  
  
  
  MTRR A2756G, SHMT C1420T, GCPII C1561T, MTRR A2756G and GNMT C1289T and RFC1 G80A polymorphisms showed significantly different prevalence between different groups analyzed. No significant differences were seen in the distribution of other polymorphisms.
  
  
  
  The study gives a clue for the possible selection of specific polymorphisms in the genes involved in the folate metabolism pathway by malaria parasite.
authors.affiliation: Department of Hemostasis and Thrombosis, National Institute of Immunohaematology (ICMR), New Multistoreyed Building, KEM Hospital, Parel, Mumbai.
authors.forename: Darshana
authors.initials: D
authors.lastname: Mirgal
authors.affiliation: Surat Raktadan Kendra and Research Center, Gujarat.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: Regional Medical Research Centre (ICMR), Dibrugarh, Assam.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Mahanta
authors.affiliation: Regional Medical Research Centre (ICMR), Dibrugarh, Assam.
authors.forename: Prafulla
authors.initials: P
authors.lastname: Dutta
authors.affiliation: Department of Hemostasis and Thrombosis, National Institute of Immunohaematology (ICMR), New Multistoreyed Building, KEM Hospital, Parel, Mumbai shrimatishetty@yahoo.com.
authors.forename: Shrimati
authors.initials: S
authors.lastname: Shetty
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D003541:Cystathionine beta-Synthase / Q000235:genetics; D019353:Endemic Diseases; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D043425:Glutamate Carboxypeptidase II / Q000235:genetics; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics; D050938:Glycine N-Methyltransferase / Q000235:genetics; D006801:Humans; D007194:India; D008288:Malaria / Q000235:genetics*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D058978:Reduced Folate Carrier Protein / Q000235:genetics; D012641:Selection, Genetic
chemical_list: D000954:Antigens, Surface; D058978:Reduced Folate Carrier Protein; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D050938:Glycine N-Methyltransferase; D012696:Glycine Hydroxymethyltransferase; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D003541:Cystathionine beta-Synthase
keywords: Folate metabolism pathway polymorphisms; India; MTHFR; Malaria; Selection