title: Study on association between genetic polymorphisms of haem oxygenase-1, tumour necrosis factor, cadmium exposure and malaria pathogenicity and severity.
abstract: BACKGROUND
  Malaria is the most important public health problems in tropical and sub-tropical countries. Haem oxygenase (HO) enzyme and the pro-inflammatory cytokine tumour necrosis factor (TNF) have been proposed as one of the factors that may play significant role in pathogenicity/severity of malaria infection. HO is the enzyme of the microsomal haem degradation pathway that yields biliverdin, carbon monoxide, and iron. In this study, the association between malaria disease pathogenicity/severity and (GT)n repeat polymorphism in the promoter region of the inducible HO-1 including the effect of cadmium exposure (potent inducer of HO-1 transcription) as well as polymorphism of TNF were investigated.
  
  
  METHODS
  Blood samples were collected from 329 cases non-severe malaria with acute uncomplicated Plasmodium falciparum malaria (UM) and 80 cases with Plasmodium vivax malaria (VM), and 77 cases with severe or cerebral malaria (SM) for analysis of genetic polymorphisms of HO-1 and TNF and cadmium levels. These patients consisted of 123 (25.3%) Thai, 243 (50.0%) Burmese and 120 (24.7%) Karen who were present at Mae Sot General Hospital, Mae Sot, Tak Province, Thailand.
  
  
  RESULTS
  The number of (GT)n repeats of the HO-1 gene in all patients varied between 16 and 39 and categorized to short (S), medium (M) and long (L) GTn repeats. The genotype of (GT)n repeat of HO-1 was found to be significantly different among the three ethnic groups of patients. Significantly higher frequency of S/L genotype was found in Burmese compared with Thai patients, while significantly lower frequencies of S/S and M/L but higher frequency of M/M genotype was observed in Burmese compared with Karen patients. No significant association between HO-1 and TNF polymorphisms including the inducing effect of cadmium and malaria pathogenicity/severity was observed.
  
  
  CONCLUSIONS
  Difference in the expression of HO-1 genotype in different ethnic groups may contribute to different severity of malaria disease. With this limited sample size, the finding of the lack of association between malaria disease pathogenicity/severity genetic polymorphisms of HO-1 (GT)n repeat as well as TNF observed in this study may not entirely exclude their possible link with malaria disease pathogenicity/severity. Further study in larger sample size is required.
authors.affiliation: Pharmacology and Toxicology Unit, Graduate Programme in Biomedical Sciences, Thammasat University, Pathumthani, Thailand.
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Kuesap
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Ronnatrai
authors.initials: R
authors.lastname: Ruangweerayut
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002104:Cadmium / Q000633:toxicity*; D002648:Child; D002675:Child, Preschool; D005006:Ethnicity; D020022:Genetic Predisposition to Disease; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000473:pathology*; D016780:Malaria, Vivax / Q000473:pathology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000302:isolation & purification; D010966:Plasmodium vivax / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index; D013785:Thailand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; D002104:Cadmium; D006419:Heme Oxygenase (Decyclizing)