Abstract 352: A Common Hypofunctional Genetic Variant of GPER: Increased Blood Pressure in Female Carriers and Increased Expression in Female Hypertensive Patients
Bibliographic record
Abstract
Activation of the aldosterone/estrogen GPCR, GPER, has been linked to vasodepressor effects. Further, genetic deletion of GPER in one mouse model has been linked to increased blood pressure in female but not male mice. However, the significance of GPER regulation for chronic blood pressure control in humans is unknown. To examine this question we determined the functional significance of expression of a common missense single nucleotide variant of GPER, P16L, and the impact of its expression on blood pressure and in the development of hypertension. Expression of the GPER P16L variant in rat aortic vascular smooth muscle cells vs. expression of wild type (WT) GPER, was associated with a significant decrease in G1 (1μM, a GPER agonist)-mediated ERK activation and G1-mediated inhibition of apoptosis. In normotensive subjects, expression of this hypofunctional GPER variant (allele frequency=22%) paralleled an increase in mean arterial blood pressure in females [P16/P16: 80±1 mmHg (n=236) vs P16L carriers: 82±1 mmHg (n=156), p<0.05] but not in males. To validate the importance of expression of the GPER P16L variant on the development of hypertension, we compared the allele frequency in normotensive vs. hypertensive subjects, the latter recruited from patients referred to a tertiary care level hypertension clinic (n=151). In this hypertensive patient population, the P16L allele frequency was increased in female patients with hypertension (1.4 fold, p<0.05 vs. allele frequency in normotensives) but was not increased in hypertensive males. In summary, we have determined that the common genetic variant, P16L GPER, is hypofunctional and that expression of this missense single nucleotide polymorphism is associated with increased blood pressure in normotensive subjects and with an increased frequency in hypertensive female but not male patients. Cumulatively, these data suggest that in females, impaired GPER function is associated with increased blood pressure and risk of hypertension.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".