Blood lead levels, iron metabolism gene polymorphisms and homocysteine: A gene-environment interaction study

Kyoung Nam Kim, Mee Ri Lee, Youn Hee Lim, Yun-Chul Hong

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)899-904
Number of pages6
JournalOccupational and Environmental Medicine
Volume74
Issue number12
DOIs
StatePublished - 1 Dec 2017

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Gene-Environment Interaction
Homocysteine
Single Nucleotide Polymorphism
Iron
Genes
Joints
Lead
Genetic Polymorphisms
Health

Keywords

  • Blood Lead Levels
  • Gene-environment Interaction
  • Homocysteine
  • Single-nucleotide Polymorphism

Cite this

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title = "Blood lead levels, iron metabolism gene polymorphisms and homocysteine: A gene-environment interaction study",
abstract = "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.",
keywords = "Blood Lead Levels, Gene-environment Interaction, Homocysteine, Single-nucleotide Polymorphism",
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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.

In: Occupational and Environmental Medicine, Vol. 74, No. 12, 01.12.2017, p. 899-904.

Research output: Contribution to journalArticle

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

PY - 2017/12/1

Y1 - 2017/12/1

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 - Blood Lead Levels

KW - Gene-environment Interaction

KW - Homocysteine

KW - Single-nucleotide Polymorphism

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DO - 10.1136/oemed-2017-104375

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AN - SCOPUS:85037160968

VL - 74

SP - 899

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JO - Occupational and Environmental Medicine

JF - Occupational and Environmental Medicine

SN - 1351-0711

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