title: Effect modification by vitamin D receptor genetic polymorphisms in the association between cumulative lead exposure and pulse pressure: a longitudinal study.
abstract: BACKGROUND
  Although the association between lead and cardiovascular disease is well established, potential mechanisms are still poorly understood. Calcium metabolism plays a role in lead toxicity and thus, vitamin D receptor (VDR) polymorphisms have been suggested to modulate the association between lead and health outcomes. We investigated effect modification by VDR genetic polymorphisms in the association between cumulative lead exposure and pulse pressure, a marker of arterial stiffness.
  
  
  METHODS
  We examined 727 participants (3,100 observations from follow-ups from 1991 to 2011) from the Normative Aging Study (NAS), a longitudinal study of aging. Tibia and patella bone lead levels were measured using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNPs) in the VDR gene, Bsm1, Taq1, Apa1, and Fok1, were genotyped. Linear mixed effects models with random intercepts were implemented to take into account repeated measurements.
  
  
  RESULTS
  Adjusting for potential confounders, pulse pressure was 2.5 mmHg (95% CI: 0.4-4.7) and 1.9 mmHg (95% CI: 0.1-3.8) greater per interquartile range (IQR) increase in tibia lead (15 μg/g) and patella lead (20 μg/g), respectively, in those with at least one minor frequency allele in Bsm1 compared with those with major frequency allele homozygotes. The observed interaction effect between bone lead and the Bsm1 genotype persists over time during the follow-up. Similar results were observed in effect modification by Taq1.
  
  
  CONCLUSIONS
  This study suggests that subjects with the minor frequency alleles of VDR Bsm1 or Taq1 may be more susceptible to cumulative lead exposure-related elevated pulse pressure.
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
authors.forename: Min A
authors.initials: MA
authors.lastname: Jhun
authors.affiliation: Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
authors.forename: Howard
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Weisskopf
authors.affiliation: School of Health Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: Linda H
authors.initials: LH
authors.lastname: Nie
authors.affiliation: Veterans Affairs Boston Healthcare System and Boston University School of Medicine & Public Health, Boston, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.affiliation: Veterans Affairs Boston Healthcare System and Boston University School of Medicine & Public Health, Boston, MA, USA.
authors.forename: Pantel S
authors.initials: PS
authors.lastname: Vokonas
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA. sungkyun@umich.edu.
authors.forename: Sung Kyun
authors.initials: SK
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001900:Boston; D002118:Calcium / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology*; D004781:Environmental Exposure / Q000032:analysis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007854:Lead / Q000633:toxicity*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010329:Patella / Q000737:chemistry; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism*; D013977:Tibia / Q000737:chemistry; D014807:Vitamin D / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; D007854:Lead; D002118:Calcium