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 language | English |
|---|---|
| Pages (from-to) | 899-904 |
| Number of pages | 6 |
| Journal | Occupational and Environmental Medicine |
| Volume | 74 |
| Issue number | 12 |
| DOIs | |
| State | Published - 1 Dec 2017 |
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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 journal › Article
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
UR - http://www.scopus.com/inward/record.url?scp=85037160968&partnerID=8YFLogxK
U2 - 10.1136/oemed-2017-104375
DO - 10.1136/oemed-2017-104375
M3 - Article
C2 - 28775131
AN - SCOPUS:85037160968
VL - 74
SP - 899
EP - 904
JO - Occupational and Environmental Medicine
JF - Occupational and Environmental Medicine
SN - 1351-0711
IS - 12
ER -