Chronic Kidney Disease: Combined Effects of Gene Polymorphisms of Tissue Inhibitors of Metalloproteinase 3, Total Urinary Arsenic, and Blood Lead Concentration

Ying-Chin Lin, Ya-Li Huang, Horng-Sheng Shiue, Sheng-Lun Hsu and Yu-Mei Hsueh ()
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Ying-Chin Lin: Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan
Ya-Li Huang: Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Horng-Sheng Shiue: Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Sheng-Lun Hsu: Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan
Yu-Mei Hsueh: Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan

IJERPH, 2023, vol. 20, issue 3, 1-10

Abstract: 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.

Keywords: tissue inhibitor of metalloproteinase 3; polymorphisms; total urinary arsenic; blood lead; chronic kidney disease (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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