Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study
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Blood lead levels, iron metabolism gene polymorphisms and homocysteine : a gene-environment interaction study. / Kim, Kyoung-Nam; Lee, Mee-Ri; Lim, Youn-Hee; Hong, Yun-Chul.
I: Occupational and Environmental Medicine, Bind 74, Nr. 12, 2017, s. 899-904.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Blood lead levels, iron metabolism gene polymorphisms and homocysteine
T2 - a gene-environment interaction study
AU - Kim, Kyoung-Nam
AU - Lee, Mee-Ri
AU - Lim, Youn-Hee
AU - Hong, Yun-Chul
N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PY - 2017
Y1 - 2017
N2 - OBJECTIVES: Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms.METHODS: From a community-based prospective cohort, we analysed 386 participants (aged 41-71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes (TF, HFE, CBS, BHMT and MTR) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes.RESULTS: Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (p<0.0083). Seven SNPs in the MTHFR gene were associated with homocysteine levels at an α-level of 0.05, but the associations did not persist after Bonferroni correction. These SNPs did not show interactions with lead levels.CONCLUSIONS: Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association.
AB - OBJECTIVES: Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms.METHODS: From a community-based prospective cohort, we analysed 386 participants (aged 41-71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes (TF, HFE, CBS, BHMT and MTR) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes.RESULTS: Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (p<0.0083). Seven SNPs in the MTHFR gene were associated with homocysteine levels at an α-level of 0.05, but the associations did not persist after Bonferroni correction. These SNPs did not show interactions with lead levels.CONCLUSIONS: Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association.
KW - Adult
KW - Aged
KW - Female
KW - Gene-Environment Interaction
KW - Genetic Predisposition to Disease
KW - Genotype
KW - Homocysteine/blood
KW - Humans
KW - Iron/metabolism
KW - Lead/adverse effects
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Prospective Studies
KW - Risk Factors
KW - Transferrin/genetics
U2 - 10.1136/oemed-2017-104375
DO - 10.1136/oemed-2017-104375
M3 - Journal article
C2 - 28775131
VL - 74
SP - 899
EP - 904
JO - Occupational and Environmental Medicine
JF - Occupational and Environmental Medicine
SN - 1351-0711
IS - 12
ER -
ID: 230068794