Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study.
<h4>Background</h4>Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD), hemochromatosis (HFE), heme oxygenase-1 (HMOX1), vitamin D receptor (VDR), glutathione S-transferase (GST) supergene family (GSTP1, GS...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0161472&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849467422883446784 |
|---|---|
| author | Ning Ding Xin Wang Marc G Weisskopf David Sparrow Joel Schwartz Howard Hu Sung Kyun Park |
| author_facet | Ning Ding Xin Wang Marc G Weisskopf David Sparrow Joel Schwartz Howard Hu Sung Kyun Park |
| author_sort | Ning Ding |
| collection | DOAJ |
| description | <h4>Background</h4>Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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. |
| format | Article |
| id | doaj-art-2277ae0a43664bc988ebfb521f6f85a3 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-2277ae0a43664bc988ebfb521f6f85a32025-08-20T03:26:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016147210.1371/journal.pone.0161472Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study.Ning DingXin WangMarc G WeisskopfDavid SparrowJoel SchwartzHoward HuSung Kyun Park<h4>Background</h4>Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0161472&type=printable |
| spellingShingle | Ning Ding Xin Wang Marc G Weisskopf David Sparrow Joel Schwartz Howard Hu Sung Kyun Park Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study. PLoS ONE |
| title | Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study. |
| title_full | Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study. |
| title_fullStr | Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study. |
| title_full_unstemmed | Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study. |
| title_short | Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study. |
| title_sort | lead related genetic loci cumulative lead exposure and incident coronary heart disease the normative aging study |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0161472&type=printable |
| work_keys_str_mv | AT ningding leadrelatedgeneticlocicumulativeleadexposureandincidentcoronaryheartdiseasethenormativeagingstudy AT xinwang leadrelatedgeneticlocicumulativeleadexposureandincidentcoronaryheartdiseasethenormativeagingstudy AT marcgweisskopf leadrelatedgeneticlocicumulativeleadexposureandincidentcoronaryheartdiseasethenormativeagingstudy AT davidsparrow leadrelatedgeneticlocicumulativeleadexposureandincidentcoronaryheartdiseasethenormativeagingstudy AT joelschwartz leadrelatedgeneticlocicumulativeleadexposureandincidentcoronaryheartdiseasethenormativeagingstudy AT howardhu leadrelatedgeneticlocicumulativeleadexposureandincidentcoronaryheartdiseasethenormativeagingstudy AT sungkyunpark leadrelatedgeneticlocicumulativeleadexposureandincidentcoronaryheartdiseasethenormativeagingstudy |