Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study

Details

• Personal Author:
  Ding N ; Hu H ; Park SK ; Schwartz J ; Sparrow D ; Wang X ; Weisskopf MG
• Description:
  BACKGROUND: Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the Delta-aminolevulinic acid dehydratase (ALAD), hemochromatosis (HFE), heme oxygenase-1 (HMOX1), vitamin D receptor (VDR), glutathione S-transferase (GST) supergene family (GSTP1, GSTT1, GSTM1), apolipoprotein E (APOE),angiotensin II receptor-1 (AGTR1) and angiotensinogen (AGT) genes, are believed to alter toxicokinetics and/or toxicodynamics of lead. OBJECTIVES: We assessed possible effect modification by genetic polymorphisms in ALAD, HFE, HMOX1, VDR, GSTP1, GSTT1, GSTM1, APOE, AGTR1 and AGT individually and as the genetic risk score (GRS) on the association between cumulative lead exposure and incident coronary heart disease (CHD) events. METHODS: We used K-shell-X-ray fluorescence to measure bone lead levels. GRS was calculated on the basis of 22 lead-related loci. We constructed Cox proportional hazard models to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CHD. We applied inverse probability weighting to account for potential selection bias due to recruitment into the bone lead sub-study. RESULTS: Significant effect modification was found by VDR, HMOX1, GSTP1, APOE, and AGT genetic polymorphisms when evaluated individually. Further, the bone lead-CHD associations became larger as GRS increases. After adjusting for potential confounders, a HR of CHD was 2.27 (95%CI: 1.50-3.42) with 2-fold increase in patella lead levels, among participants in the top tertile of GRS. We also detected an increasing trend in HRs across tertiles of GRS (p-trend = 0.0063). CONCLUSIONS: Our findings suggest that lead-related loci as a whole may play an important role in susceptibility to lead-related CHD risk. These findings need to be validated in a separate cohort containing bone lead, lead-related genetic loci and incident CHD data. [Description provided by NIOSH]
• Subjects:
  Aging Cardiovascular Diseases Cardiovascular System Chemistry Environmental Exposure Genetics Lead Men Occupational Health Risk Assessment Risk Factors Safety Women

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• Keywords:
  Age Groups Bone Structure Chemical Properties Environmental Exposure Exposure Levels Heart Disease Humans Lead Compounds Physiology Risk Factors
• ISSN:
  1932-6203
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; Michigan ; OSHA Region 1 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  11
• NIOSHTIC Number:
  nn:20050166
• Citation:
  PLoS One 2016 Sep; 11:e0161472
• Contact Point Address:
  Sung Kyun Park, Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America
• Email:
  sungkyun@umich.edu
• CAS Registry Number:
  Lead (CAS RN 7439-92-1)
• Federal Fiscal Year:
  2016
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  PLoS One
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:efe1addcda2bcabb1258f06ea3b5dcd893cc508d2f57461c2ef17e7cf244a7e6d67bfce15128a0b372ddbabe450771de389abb56770f7e726a89407aa11abd36
• Download URL:
  https://stacks.cdc.gov/view/cdc/210638/cdc_210638_DS1.pdf
• File Type:
  [PDF - 291.01 KB ]