Effect modification by Vitamin D receptor genetic polymorphisms in the association between lead and pulse pressure
Bibliographic record
Abstract
Lead may increase the risk of cardiovascular disease by increasing blood pressure and worsening arterial stiffness through calcium metabolism. Vitamin D receptor (VDR) plays an important role in lead metabolism. However, the role of VDR genetic polymorphisms in the association between lead and pulse pressure has not been studied yet. We investigated effect modification by the VDR gene in the association between cumulative lead exposure and pulse pressure, a marker of arterial stiffness. We examined 727 participants in the Normative Aging Study. Tibia and patella bone lead levels were measured using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNP) in VDR gene, Bsm1 (rs1544410), Taq1 (rs731236), Asp1 (rs7975232), Fok1 (rs1073581), were genotyped. To account for the repeated measurements, linear mixed effects models were implemented. The effects of lead, SNP, and lead by SNP interaction were investigated adjusting for age at baseline, time since baseline, body mass index, smoking, alcohol intake, diabetes status, family history of hypertension, and education. Age by SNP interaction was also included in the model considering different effect of genetic polymorphism by age. The participants with at least a copy of the minor allele in Bsm1 (n=442) had a stronger association between bone lead and pulse pressure than those with major alleles (n=238) (? for the interaction term=0.18mmHg (95% CI:0.04-0.32,p=0.01) for tibia lead; ?=0.10 (95% CI:0.01-0.19,p=0.04) for patella lead). The participants with at least a copy of the minor allele in Taq1 (n=481) also had a stronger association between bone lead and pulse pressure compared to the others (n=242) (?=0.14 (95% CI:-0.001-0.27,p=0.05) for tibia lead; ?=0.10 (95% CI:0.01-0.19,p=0.02) for patella lead). There was no significant effect modification by Fok1 or Asp1. The effects of genetic mutations on pulse pressure differed by age. This study suggests that subjects with the minor allele of Bsm1 or Taq1 are more susceptible to cumulative lead exposure-related elevated pulse pressure.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.006 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".