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; Yu-Mei Hsueh

doi:10.3390/ijerph20031886

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

Int J Environ Res Public Health. 2023 Jan 19;20(3):1886. doi: 10.3390/ijerph20031886.

Authors

Ying-Chin Lin^{1

2

3}, Ya-Li Huang⁴, Horng-Sheng Shiue⁵, Sheng-Lun Hsu¹, Yu-Mei Hsueh^{1

4}

Affiliations

¹ Department of Family Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan.
² Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
³ Department of Occupational Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan.
⁴ Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
⁵ Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.

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: blood lead; chronic kidney disease; polymorphisms; tissue inhibitor of metalloproteinase 3; total urinary arsenic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arsenic* / urine
Cadmium
Case-Control Studies
Humans
Lead
Polymorphism, Genetic
Renal Insufficiency, Chronic* / genetics
Renal Insufficiency, Chronic* / urine
Selenium*

Substances

Arsenic
Cadmium
Lead
Selenium
TIMP3 protein, human

Grants and funding

This study was supported by grants from the Ministry of Science and Technology of Taiwan (MOST 106-2314-B-038-066, MOST 107-2320-B-039-010, MOST 106-2314-B-002-235-MY3, MOST 107-2314-B-038-073, MOST 108-2314-B-038-089, MOST 109-2314-B-038-081, MOST 109-2314-B-038-067, MOST 110-2314-B-038-054, and MOST 111-2314-B-038-052).