Effect modification by vitamin D receptor genetic polymorphisms in the association between cumulative lead exposure and pulse pressure: a longitudinal studyReport as inadecuate




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Environmental Health

, 14:5

First Online: 13 January 2015Received: 08 July 2014Accepted: 27 December 2014DOI: 10.1186-1476-069X-14-5

Cite this article as: Jhun, M.A., Hu, H., Schwartz, J. et al. Environ Health 2015 14: 5. doi:10.1186-1476-069X-14-5

Abstract

BackgroundAlthough 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.

MethodsWe 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.

ResultsAdjusting 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.

ConclusionsThis 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.

KeywordsLead Vitamin D receptor Gene by environmental interaction A longitudinal study AbbreviationsBMIBody mass index

CVDCardiovascular diseases

DBPDiastolic blood pressure

HDLHigh-density lipoprotein

IQRInterquartile range

KXRFK-x-ray fluorescence instrument

NASNormative aging study

NTPNational toxicology program

SBPSystolic blood pressure

SNPSingle nucleotide polymorphism

VDRVitamin D receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-069X-14-5 contains supplementary material, which is available to authorized users.

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Author: Min A Jhun - Howard Hu - Joel Schwartz - Marc G Weisskopf - Linda H Nie - David Sparrow - Pantel S Vokonas - Sung Kyun

Source: https://link.springer.com/







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