The protective effect of rs373863828 on type 2 diabetes does not operate through a body composition pathway in adult Samoans.

Autor: Hawley NL; Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut, USA., Duckham RL; Institute of Physical Activity and Nutrition, Deakin University, Melbourne, Victoria, Australia.; Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne, Western Health, St Albans, Victoria, Australia., Carlson JC; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Naseri T; Ministry of Health, Apia, Samoa., Reupena MS; Lutia I Puava Ae Mapu I Fagalele, Apia, Samoa., Lameko V; Oceania University of Medicine, Apia, Samoa., Pomer A; Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut, USA., Wetzel A; International Health Institute, Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, USA., Selu M; Obesity, Lifestyle and Genetic Adaptations Study Group, Apia, Samoa., Lupematisila V; Obesity, Lifestyle and Genetic Adaptations Study Group, Apia, Samoa., Unasa F; Obesity, Lifestyle and Genetic Adaptations Study Group, Apia, Samoa., Vesi L; Obesity, Lifestyle and Genetic Adaptations Study Group, Apia, Samoa., Fatu T; Obesity, Lifestyle and Genetic Adaptations Study Group, Apia, Samoa., Unasa S; Obesity, Lifestyle and Genetic Adaptations Study Group, Apia, Samoa., Faasalele-Savusa K; Obesity, Lifestyle and Genetic Adaptations Study Group, Apia, Samoa., Rivara AC; Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, Connecticut, USA., Russell E; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Delany JP; AdventHealth, Translational Research Institute, Orlando, Florida, USA., Viali S; School of Medicine, National University of Samoa, Apia, Samoa., Kershaw EE; Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Minster RL; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Weeks DE; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., McGarvey ST; International Health Institute, Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, USA.
Jazyk: angličtina
Zdroj: Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2022 Dec; Vol. 30 (12), pp. 2468-2476. Date of Electronic Publication: 2022 Oct 25.
DOI: 10.1002/oby.23559
Abstrakt: Objective: The 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.
Methods: This 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.
Results: Among 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).
Conclusions: The 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.
(© 2022 The Obesity Society.)
Databáze: MEDLINE
Externí odkaz: