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Original Article
Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study
  1. Kyoung-Nam Kim1,2,
  2. Mee-Ri Lee1,
  3. Youn-Hee Lim3,4,
  4. Yun-Chul Hong1,3,4
  1. 1 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
  2. 2 Public Health Medical Service, Seoul National University Hospital, Seoul, South Korea
  3. 3 Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, South Korea
  4. 4 Environmental Health Center, Seoul National University College of Medicine, Seoul, South Korea
  1. Correspondence to Dr Yun-Chul Hong, Department of Preventive Medicine, Seoul National University College of Medicine, 28 Yongo Dong, Chongno Gu, Seoul 110 799, Republic of Korea; ychong1{at}


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.

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

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  • Contributors All authors equally contributed in designing the study. KNK and YCH analysed the data and wrote the manuscript. MRL and YHL revised the manuscript. All authors approved the version to be published.

  • Funding This study was supported by grants from the Korea Centers for Disease Control, Republic of Korea (2001-347-6111-221, 2002-347-6111-221, 2003-347-6111-221, 2004-E71001-00, 2005-E71001-00, 2006-E71005-00, 2007-E71001-00 and 2008-E71001-00). This study was also supported in part by the R&D Program for Society of the National Research Foundation funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (2014M3C8A5030619). The funding bodies had no role in the study design, data collection, analysis, interpretation of results and manuscript writing.

  • Competing interests None declared.

  • Ethics approval The Institutional Review Board of Seoul National University Hospital approved the study protocol (C-1306-046-495).

  • Provenance and peer review Not commissioned; externally peer reviewed.