The Mediation Effects of Aluminum in Plasma and Dipeptidyl Peptidase Like Protein 6 (DPP6) Polymorphism on Renal Function via Genome-Wide Typing Association

Ting-Hao Chen, Chen-Cheng Yang, Kuei-Hau Luo, Chia-Yen Dai, Yao-Chung Chuang and Hung-Yi Chuang
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Ting-Hao Chen: Department of Public Health and Environmental Medicine, Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Chen-Cheng Yang: Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Kuei-Hau Luo: Department of Public Health and Environmental Medicine, Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Chia-Yen Dai: Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Yao-Chung Chuang: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
Hung-Yi Chuang: Department of Public Health and Environmental Medicine, Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

IJERPH, 2021, vol. 18, issue 19, 1-12

Abstract: Aluminum (Al) toxicity is related to renal failure and the failure of other systems. Although there were some genome-wide association studies (GWAS) in Australia and England, there were no GWAS about Han Chinese to our knowledge. Thus, this research focused on using whole genomic genotypes from the Taiwan Biobank for exploring the association between Al concentrations in plasma and renal function. Participants, who underwent questionnaire interviews, biomarkers, and genotyping, were from the Taiwan Biobank database. Then, we measured their plasma Al concentrations with ICP-MS in the laboratory at Kaohsiung Medical University. We used this data to link genome-wide association (GWA) tests while looking for candidate genes and associated plasma Al concentration to renal function. Furthermore, we examined the path relationship between Single Nucleotide Polymorphisms (SNPs), Al concentrations, and estimated glomerular filtration rates (eGFR) through the mediation analysis with 3000 replication bootstraps. Following the principles of GWAS, we focused on three SNPs within the dipeptidyl peptidase-like protein 6 ( DPP6 ) gene in chromosome 7, rs10224371, rs2316242, and rs10268004, respectively. The results of the mediation analysis showed that all of the selected SNPs have indirectly affected eGFR through a mediation of Al concentrations. Our analysis revealed the association between DPP6 SNPs, plasma Al concentrations, and eGFR. However, further longitudinal studies and research on mechanism are in need. Our analysis was still be the first study that explored the association between the DPP6 , SNPs, and Al in plasma affecting eGFR.

Keywords: aluminum; Taiwan Biobank; estimated glomerular filtration rate; genome-wide association; mediation analysis; dipeptidyl peptidase-like protein 6 (DPP6) gene (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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