HFE H63D polymorphism as a modifier of the effect of cumulative lead exposure on pulse pressure: The normative aging study

Aimin Zhang, Sung Kyun Park, Robert O. Wright, Marc G. Weisskopf, Bhramar Mukherjee, Huiling Nie, David Sparrow, Howard Hu

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Background: Cumulative lead exposure is associated with a widened pulse pressure (PP; the difference between systolic and diastolic blood pressure), a marker of arterial stiffness and a predictor of cardiovascular disease. Polymorphisms in the hemochromatosis gene (HFE) have been shown to modify the impact of cumulative lead exposure on measures of adult cognition and cardiac function. Objectives: We examined whether the HFE mutations modify the impact of lead on PP in community-dwelling older men.Methods: We examined 619 participants with a total of 1,148 observations of PP from a substudy of bone lead levels (a measure of cumulative exposure, measured by in vivo K-shell X-ray fluorescence) and health in the Normative Aging Study between 1991 and 2001. Linear mixed-effects regression models with random intercepts were constructed. Results: Of the 619 subjects, 138 and 72 carried the HFE H63D and C282Y variants, respectively. After adjusting for age; education; alcohol intake; smoking; daily intakes of calcium, sodium, and potassium; total calories; family history of hypertension; diabetes; height; heart rate; high-density lipoprotein (HDL); total cholesterol:HDL ratio; and waist circumference, baseline bone lead levels were associated with steeper increases in PP in men with at least one H63D allele (p-interaction = 0.03 for tibia and 0.02 for patella) compared with men with only the wild types or C282Y variant. Conclusions: The HFE H63D polymorphism, but not the C282Y mutation, appears to enhance susceptibility to the deleterious impact of cumulative lead on PP, possibly via prooxidative or pro-inflammatory mechanisms.

Original languageEnglish
Pages (from-to)1261-1266
Number of pages6
JournalEnvironmental Health Perspectives
Issue number9
StatePublished - Sep 2010
Externally publishedYes


  • Gene-environment interaction
  • H63D mutation
  • Hemochromatosis gene
  • Lead exposure
  • Pulse pressure


Dive into the research topics of 'HFE H63D polymorphism as a modifier of the effect of cumulative lead exposure on pulse pressure: The normative aging study'. Together they form a unique fingerprint.

Cite this