title: Study on the association between environmental cadmium exposure, cytochrome P450-mediated 20-HETE, heme-oxygenase-1 polymorphism and hypertension in Thai population residing in a malaria endemic areas with cadmium pollution.
abstract: The aims of the study were to investigate (i) the effects of environmental cadmium (Cd) on hypertension, biological markers of renal dysfunction and renal cytochrome P450-mediated arachidonate metabolism; and (ii) the association between genetic polymorphism of heme oxygenase-1 (HO-1) and hypertension and Cd-induced renal injury in the exposed Thai population. The study was conducted in adult subjects residing in Cd-contaminated malaria endemic areas of Mae Sot District, Thailand. All subjects were randomly selected and consistently distributed for sex, age and residential areas. Blood and urinary Cd levels were not significantly different between the case (hypertensive) and control (matched-pair normotensive) groups. While other renal dysfunction biomarkers were comparable between the two groups, urinary microalbumin, urinary 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE) and serum creatinine were siginificantly higher in the hypertensive group. Only N-acetyl-β-glucosaminidase (NAG) showed positive correlation with Cd in hypertensive and normotensive group. With respect to heme oxygenase-1 (HO-1) polymorphism, the frequencies of (GT)(n) alleles were similar in both case and control groups. The frequency of SL genotype was significantly higher in the control group, whereas the frequency of ML genotype was significantly higher in the case group. Although no significant difference between 20-HETE and NAG levels in various HO-1 genotypes was found, a trend of increase in 20-HETE and NAG levels was observed in subjects carrying longer (GT)(n) repeats. Results from the present study provide no clear evidence on the direct effects of environmental Cd on high blood pressure development in the non-occupational exposed Thai population. Furthermore, the indirect effect of Cd through HO-1 (genetic polymorphism and prevalence of long GT(n) repeats) and 20-HETE was inconclusive. Based on the data obtained in the present investigation further studies should be performed which use a larger sample size and effectively control for confounding. This should provide more definitive evidence of the relationship between Cd exposure and high blood pressure.
authors.affiliation: Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand.
authors.forename: Kanyarat
authors.initials: K
authors.lastname: Boonprasert
authors.forename: Ronnatrai
authors.initials: R
authors.lastname: Ruengweerayut
authors.forename: Soisungwan
authors.initials: S
authors.lastname: Satarug
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D002104:Cadmium / Q000009:adverse effects* / Q000032:analysis* / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D019353:Endemic Diseases; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis*; D004784:Environmental Monitoring; D004787:Environmental Pollution / Q000009:adverse effects* / Q000032:analysis*; D062665:Epidemiological Monitoring; D005260:Female; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced* / Q000453:epidemiology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology; D007677:Kidney Function Tests; D008288:Malaria / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects; D013785:Thailand / Q000453:epidemiology
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D002104:Cadmium; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D051547:Heme Oxygenase-1