Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand.
Environ Toxicol Pharmacol. 2011 May;31(3):416-26. doi: 10.1016/j.etap.2011.02.003. Epub 2011 Feb 12.
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.
(i)环境镉（Cd）对高血压、肾功能生物标志物和肾细胞色素 P450 介导的花生四烯酸代谢的影响；(ii)血红素加氧酶-1（HO-1）的遗传多态性与高血压和 Cd 诱导的暴露于泰国人群的肾损伤之间的关联。该研究在泰国 Mae Sot 区镉污染疟疾流行地区的成年受试者中进行。所有受试者均随机选择，并根据性别、年龄和居住区域均匀分布。病例组（高血压）和对照组（配对的正常血压）的血液和尿液 Cd 水平无显著差异。虽然两组的其他肾功能生物标志物无差异，但高血压组的尿微量白蛋白、尿 20-羟基-5,8,11,14-二十碳四烯酸（20-HETE）和血清肌酐明显升高。只有 N-乙酰-β-氨基葡萄糖苷酶（NAG）在高血压和正常血压组与 Cd 呈正相关。关于血红素加氧酶-1（HO-1）多态性，病例组和对照组（GT）（n）等位基因的频率相似。SL 基因型在对照组中的频率明显较高，而 ML 基因型在病例组中的频率明显较高。尽管在各种 HO-1 基因型中未发现 20-HETE 和 NAG 水平之间存在显著差异，但在携带较长（GT）（n）重复的个体中观察到 20-HETE 和 NAG 水平升高的趋势。本研究结果并未提供明确证据表明环境 Cd 对非职业性暴露的泰国人群高血压发展的直接影响。此外，通过 HO-1（遗传多态性和长 GT（n）重复的流行）和 20-HETE 间接影响 Cd 的作用尚无定论。基于本研究获得的数据，应进行进一步的研究，使用更大的样本量并有效地控制混杂因素。这将提供关于 Cd 暴露与高血压之间关系的更明确证据。
