ArticleObesity (Silver Spring, Md.)2022
The protective effect of rs373863828 on type 2 diabetes does not operate through a body composition pathway in adult Samoans.
Article in Obesity (Silver Spring, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Type 2 Diabetes Prevalence, Control and Management within Fiji,Kiribati, Samoa, the Solomon Islands, Tonga, and Vanuatu: A ScopingReview with a Systematic Approach.Current diabetes reviews · 2024Pooled it
- NAA10 and BTRC drive CREBRF degradation in endoplasmic reticulum stress and renal tubular injury.Journal of diabetes investigation · 2026Article
- Gestational diabetes-Risk factors and outcomes among American Samoan Women (GROW): A longitudinal cohort study protocol.PloS one · 2026Article
- Gestational Diabetes - Risk Factors and Outcomes among American Samoan Women (GROW): A Longitudinal Cohort Study Protocol.medRxiv : the preprint server for health sciences · 2025Article
- Gut microbial composition and diversity varies byPhysiological genomics · 2025Article
- Advantage in Aging Cognition Associated with theGeroPsych · 2024Article
- Cellular Senescence and Extracellular Vesicles in the Pathogenesis and Treatment of Obesity-A Narrative Review.International journal of molecular sciences · 2024Review
- Multivariate analysis of a missense variant in CREBRF reveals associations with measures of adiposity in people of Polynesian ancestries.Genetic epidemiology · 2023Article
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 5 countries.
Funding
Abstract
objectiveThe aim of this study was to understand whether the paradoxical association of missense variant rs373863828 in CREB3 regulatory factor (CREBRF) with higher BMI but lower odds of diabetes is explained by either metabolically favorable body fat distribution or greater fat-free mass.
methodsThis study explored the association of the minor allele with dual-energy x-ray absorptiometry-derived body composition in n = 421 Samoans and used path analysis to examine the mediating role of fat and fat-free mass on the relationship between rs373863828 and fasting glucose.
resultsAmong females, the rs373863828 minor A allele was associated with greater BMI. There was no association of genotype with percent body fat, visceral adiposity, or fat distribution in either sex. In both females and males, lean mass was greater with each A allele: 2.16 kg/copy (p = 0.0001) and 1.73 kg/copy (p = 0.02), respectively. Path analysis showed a direct negative effect of rs373863828 genotype on fasting glucose (p = 0.004) consistent with previous findings, but also an indirect positive effect on fasting glucose operating through fat-free mass (p = 0.027).
conclusionsThe protective effect of rs373863828 in CREBRF, common among Pacific Islanders, on type 2 diabetes does not operate through body composition. Rather, the variant's effects on body size/composition and fasting glucose likely operate via different, tissue-specific mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.