Placental CCR5 polymorphisms in relation to fetal growth
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Bibliographic record
Abstract
The placenta mediates fetal growth, and its development and function are influenced by immune interactions at the maternal-fetal interface. The cysteine-cysteine chemotactic cytokine receptor type 5 ( CCR5 ) gene codes for a pro-inflammatory protein receptor expressed in the placenta on syncytiotrophoblasts and Hofbauer cells. Associations of the placental-fetal genotype at CCR5 and birth outcomes have not been examined. Furthermore, influence of CCR5 polymorphisms on nearby DNA methylation in the placenta and in the context of infection is understudied. We assessed two functional polymorphisms in CCR5 , a 32 base pair deletion (Δ32) in the open reading frame and an A/G promoter point mutation (rs1799987) in EPIC (n = 233) a cohort consisting of complicated and uncomplicated pregnancies ascertained in Vancouver BC and found that the variant alleles were associated with birth weight (p = 0.007 and p = 0.01 respectively). We validated the association of rs1799987 with birthweight (p = 0.003) in the published NICHD dataset of normative term births (n = 286). These variant associations were, however, not present in CARMA-Preg (n = 200) a cohort enriched for HIV-exposure. Interestingly, we found rs1799987 was associated with altered DNA methylation (DNAme) at multiple CpGs spanning over 275 kb, overlapping both the CCR2 and CCR5 genes. DNAme in this region was, however, not associated with birthweight. Further investigations are needed to validate the association of CCR5 variants with fetal growth. Such studies must consider the population structure and demographics, as well as the large haplotype blocks spanning this region, which make it difficult to assign a causal relationship to specific variants. • The CCR5 gene codes for a pro-inflammatory protein receptor expressed in placenta. • Associations of placental-fetal CCR5 genotype and birth outcomes are understudied. • We assessed placental CCR5 Δ32 and rs1799987 genotypes and birth weight. • We found that CCR5 alleles were associated with birth weight. • We found that rs1799987 was associated with altered DNA methylation.
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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 | 0.001 |
| 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 it