TY - JOUR
T1 - Iron-processing genotypes, nutrient intakes, and cadmium levels in the Normative Aging Study
T2 - Evidence of sensitive subpopulations in cadmium risk assessment
AU - Ciesielski, Timothy H.
AU - Schwartz, Joel
AU - Bellinger, David C.
AU - Hauser, Russ
AU - Amarasiriwardena, Chitra
AU - Sparrow, David
AU - Wright, Robert O.
N1 - Publisher Copyright:
© 2018
PY - 2018/10
Y1 - 2018/10
N2 - Background: Because iron and cadmium share common transport mechanisms, iron-processing protein variants such as HFE C282Y, HFE H63D, and Transferrin P570S may influence cadmium metabolism. Our aim was to evaluate associations between common HFE and Transferrin polymorphisms and toenail cadmium levels among older men. Methods: In a longitudinal cohort of men age 51–97, the Normative Aging Study (NAS), we evaluated toenail cadmium concentrations and missense single nucleotide polymorphisms (SNPs) in the HFE and Transferrin genes. We fit age-adjusted models to estimate associations between genotypes and toenail cadmium concentrations. We then considered potential interactions with smoking status, hemoglobin, and nutritional intakes known to modulate cadmium absorption. For the significant interactions, we also evaluated genotype specific effect estimates. Results: HFE and Transferrin genotypes were not associated with toenail cadmium concentrations in the main effect analyses, but there were significant interactions between HFE H63D and hemoglobin (pinteraction = 0.021), as well as HFE H63D and vitamin C intake (pinteraction = 0.048). Genotype specific effect estimates suggested: 1) an inverse relationship between hemoglobin and cadmium levels among HFE H63D homozygotes, and 2) an inverse relationship between vitamin C intake and cadmium levels that strengthens with the number of HFE H63D variant alleles a subject carries. Conclusions: These findings suggest that sensitive subpopulations defined by diet, hemoglobin level, and genotype may absorb more cadmium from their environment and thus should be considered in cadmium risk analyses. These findings are particularly relevant given the high prevalence of the H63D variant worldwide.
AB - Background: Because iron and cadmium share common transport mechanisms, iron-processing protein variants such as HFE C282Y, HFE H63D, and Transferrin P570S may influence cadmium metabolism. Our aim was to evaluate associations between common HFE and Transferrin polymorphisms and toenail cadmium levels among older men. Methods: In a longitudinal cohort of men age 51–97, the Normative Aging Study (NAS), we evaluated toenail cadmium concentrations and missense single nucleotide polymorphisms (SNPs) in the HFE and Transferrin genes. We fit age-adjusted models to estimate associations between genotypes and toenail cadmium concentrations. We then considered potential interactions with smoking status, hemoglobin, and nutritional intakes known to modulate cadmium absorption. For the significant interactions, we also evaluated genotype specific effect estimates. Results: HFE and Transferrin genotypes were not associated with toenail cadmium concentrations in the main effect analyses, but there were significant interactions between HFE H63D and hemoglobin (pinteraction = 0.021), as well as HFE H63D and vitamin C intake (pinteraction = 0.048). Genotype specific effect estimates suggested: 1) an inverse relationship between hemoglobin and cadmium levels among HFE H63D homozygotes, and 2) an inverse relationship between vitamin C intake and cadmium levels that strengthens with the number of HFE H63D variant alleles a subject carries. Conclusions: These findings suggest that sensitive subpopulations defined by diet, hemoglobin level, and genotype may absorb more cadmium from their environment and thus should be considered in cadmium risk analyses. These findings are particularly relevant given the high prevalence of the H63D variant worldwide.
KW - Absorption
KW - Cadmium
KW - Gene-environment interaction
KW - HFE
KW - Hemochromatosis
KW - Iron
KW - Metals
KW - Nutrients
KW - Risk assessment
KW - Transferrin
UR - http://www.scopus.com/inward/record.url?scp=85050464520&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2018.06.040
DO - 10.1016/j.envint.2018.06.040
M3 - Article
C2 - 30059941
AN - SCOPUS:85050464520
SN - 0160-4120
VL - 119
SP - 527
EP - 535
JO - Environment international
JF - Environment international
ER -