Exploration of divalent metal transporter 1 (DMT1) gene intronic IVS4+44C/A polymorphisms in population exposed to cadmium
Authors:   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi 11000, Thailand, Parnmen Sittiporn , Nooron Nattakarn ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Chonnakijkul Pornpanna ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Sikaphan Sujitra ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Polputpisatkul Dutsadee ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Uttawichai Chutimon ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Chankunasuka Rungsaeng ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Phatsarapongkul Sriprapa ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Thunkhamrak Chidkamon ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Nitma Unchalee ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Palakul Nisakorn ,   Toxicology Center, National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, 11000, Thailand, Rojanawiwat Archawin ,   National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi 11000, Thailand
Published: August 2024

Background: Cadmium exposure affects the expression of the DMT1 gene and the function of its transporter protein, impacting the transport and accumulation. This study investigates genetic polymorphisms to understand better the pivotal role of genetic factors in cadmium-related diseases within environmental health research. Objective: The study sought to examine the intronic IVS4+44C/A polymorphism in the divalent metal transporter 1 (DMT1) gene among individuals aged 35-60 residing in regions contaminated with cadmium. Materials and methods: Blood samples were collected from 306 genetically unrelated individuals (158 females and 148 males). The DMT1 IVS4+44C/A polymorphism was determined using restriction fragment length polymorphism (RFLP) and Sanger sequencing methods. Urinary cadmium levels were measured with graphite furnace atomic absorption spectrometry (GFAAS). Statistical analyses included Hardy-Weinberg equilibrium testing, analysis of variance (ANOVA), and student’s t-tests. Results: The geometric mean of urinary cadmium levels were significantly higher in females (4.03±4.15 µg/gm creatinine) than in males (2.62±2.73 µg/gm creatinine). Remarkably, 85% of females and 66% of males exceeded the reference values for urinary cadmium concentration set by the German Human Biomonitoring (HBM) Commission (HBM I and II). Genotype frequencies were 65.4% homozygote typical (CC), 31.0% heterozygote (CA), and 3.6% homozygote atypical (AA). The C allele frequency was 80.9%, while the A allele frequency was 19.1%. Notably, the DMT1 IVS4+44C/A polymorphism significantly influenced urinary cadmium levels, with the CA genotype showing higher levels than CC and AA genotypes. Urinary cadmium levels were also statistically increased with the presence of the A allele (A+ = CA+AA) compared to its absence (A- = CC). Furthermore, our analysis revealed that individuals with the CC genotype more frequently surpass the reference values for urinary cadmium in HBM I and II across all age groups despite their overall urinary cadmium levels not being high. Conclusion: This study indicates that the CA genotype may signify susceptibility to prolonged cadmium exposure, given its association with elevated urinary cadmium levels. Additional research is essential for a thorough grasp of the implications of DMT1 gene polymorphisms on health outcomes and for establishing monitoring measures for populations residing in cadmium-contaminated areas.