Interactive effect of angiotensin II type 1 receptor (AGT1R) polymorphisms and plasma irbesartan concentration on antihypertensive therapeutic responses to irbesartan
Bibliographic record
Abstract
BACKGROUND: To investigate the interactive effect of plasma irbesartan concentration and angiotensin II type 1 receptor (AGT1R) gene polymorphisms on blood pressure (BP) response to irbesartan treatment. METHODS: This study included 1049 Chinese hypertensive patients who were treated with daily oral 150 mg irbesartan for 4 weeks. BP at predose and 28th day of treatment and trough plasma irbesartan concentration (on 28th day of treatment) were measured. Four AGT1R gene polymorphisms (rs2640539, rs1492097, rs388915, rs5186) were genotyped. Multiple linear regression models were used to assess interactive effect of plasma irbesartan concentration and gene polymorphisms on BP response, with adjustment for covariates. RESULTS: When stratified by genotypes, patients carrying allele C of single-neucleotide polymorphism (SNP) rs5186 showed positive association between irbesartan concentration and BP response [SBP: β ± SE=6.1 ± 2.3 with false discovery rate (FDR) P=0.029; DBP: β ± SE=2.7 ± 1.0 with FDR P=0.029], but this was not seen in patients with AA genotype. There was a significant interaction between plasma irbesartan concentration and SNP rs5186 on SBP response (interaction P=0.0335) and DBP response (interaction P=0.0190). There also were significant interactions between plasma irbesartan concentration and hap3, hap5 and hap6 (constructed by four genotyped SNPs) on SBP response (FDR P<0.001), but not on DBP response. CONCLUSION: Our data suggest that AGT1R gene polymorphisms and plasma concentration of irbesartan can act interactively to modulate individual response to antihypertensive therapy using irbesartan.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".