Impact of <i>AKR1C2</i> and <i>AKR1C3</i> single nucleotide polymorphism rs28571848 in adipose tissues of individuals with severe obesity
Bibliographic record
Abstract
ABSTRACT Background Adipose tissue androgen turnover, dictated at least in part by the enzymes AKR1C2 and AKR1C3, has been linked to abdominal obesity. Recently, we investigated a single-nucleotide polymorphism (SNP) named rs28571858, that might increase AKR1C2 and AKR1C3 expression in human adipose tissue. Here, we studied the impact of rs28571848 on adipose tissue function and cardiometabolic health in bariatric surgery candidates. Methods We genotyped a sample of 2776 bariatric surgery candidates and retrospectively obtained anthropometry, blood lipid and glucose profiles, menopausal status and medication use. In a subsample of 135 individuals (62% women, age 42 years, BMI of 51 kg/m 2 ), we additionally assessed AKR1C2 and AKR1C3 expression in whole tissue by RT-qPCR. Features of adipose tissue dysfunction, such as mean adipocyte diameter and pericellular fibrosis were assessed by histological staining and semi-automated image analysis. Finally, adipose tissue AKR1C family enzyme activity was measured by fluorimetry. Results The rs28571848 SNP affected AKR1C3 expression in both subcutaneous (SAT) and visceral adipose tissue (VAT) in women only, while not altering AKR1C2 expression in either men or women. Individuals carrying the minor allele exhibited increased VAT AKR1C activity compared to those with the wildtype genotype. Analysis of blood lipid profile in the whole cohort revealed that “TT” carriers had elevated total cholesterol, LDL-cholesterol, and indices of insulin resistance. Conclusion The rs28571858 SNP increased adipose tissue AKR1C3 expression and activity in women. Increased AKR1C3 may contribute to an adipose tissue milieu that prompts lipogenesis, adversely affecting cardiometabolic health by disrupting lipid homeostasis and insulin sensitivity. NEW AND NOTEWORTHY rs28571858 has a Minor Allele Frequency (MAF) of 18.7% in a cohort of 2776 residents of Quebec, Canada. rs28571858 is associated with adipose tissue AKR1C3 expression and activity in women. Minor allele homozygotes carriers have increased total cholesterol, LDL-cholesterol, and indices of insulin resistance.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".