Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan.
Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Int J Environ Res Public Health. 2023 Jan 19;20(3):1886. doi: 10.3390/ijerph20031886.
The tissue inhibitor of metalloproteinase 3 (TIMP3) is known to be an anti-fibrotic factor. Arsenic, lead, and cadmium exposure and selenium intake may affect TIMP3 expression. The downregulation of TIMP3 expression is related to kidney fibrosis. Genotypes of TIMP3 are related to hypertension and cardiovascular diseases. Therefore, this study explored whether TIMP3 polymorphism is associated with hypertension-related chronic kidney disease (CKD). In addition, the combined effects of TIMP3 polymorphism and total urinary arsenic, blood lead and cadmium, and plasma selenium concentrations on CKD, were investigated. This was a case-control study, with 213 CKD patients and 423 age- and sex-matched controls recruited. Polymerase chain reaction-restriction fragment length polymorphism was used to determine TIMP3 gene polymorphisms. The concentrations of urinary arsenic species, plasma selenium, and blood lead and cadmium were measured. The odds ratio (OR) of CKD in the TIMP3rs9609643 GA/AA genotype was higher than that of the GG genotype at high levels of total urinary arsenic and blood lead; the OR and 95% confidence interval (CI) were 0.57 (0.31-1.05) and 0.52 (0.30-0.93), respectively, after multivariate adjustment. High blood lead levels tended to interact with the TIMP3rs9609643 GG genotype to increase the OR of CKD, and gave the highest OR (95% CI) for CKD of 5.97 (2.60-13.67). Our study supports a possible role for the TIMP3rs9609643 risk genotype combined with high total urinary arsenic or with high blood lead concentration to increase the OR of CKD.
组织金属蛋白酶抑制剂 3（TIMP3）是一种已知的抗纤维化因子。砷、铅和镉暴露以及硒摄入可能会影响 TIMP3 的表达。TIMP3 表达下调与肾脏纤维化有关。TIMP3 基因型与高血压和心血管疾病有关。因此，本研究探讨了 TIMP3 多态性是否与高血压相关的慢性肾脏病（CKD）有关。此外，还研究了 TIMP3 多态性与总尿砷、血铅和镉以及血浆硒浓度对 CKD 的联合影响。这是一项病例对照研究，共纳入 213 例 CKD 患者和 423 名年龄和性别匹配的对照者。采用聚合酶链反应-限制性片段长度多态性分析方法确定 TIMP3 基因多态性。测定尿砷形态、血浆硒和血铅及镉浓度。在高水平总尿砷和血铅的情况下，TIMP3rs9609643 GA/AA 基因型的 CKD 比值比（OR）高于 GG 基因型，多变量调整后 OR（95%置信区间）分别为 0.57（0.31-1.05）和 0.52（0.30-0.93）。高血铅水平倾向于与 TIMP3rs9609643 GG 基因型相互作用，增加 CKD 的 OR，使 CKD 的最高 OR（95%CI）为 5.97（2.60-13.67）。我们的研究支持 TIMP3rs9609643 风险基因型与高水平总尿砷或高水平血铅浓度相结合可能增加 CKD 的 OR。
