The minor allele of the CREBRF rs373863828 p.R457Q coding variant is associated with reduced levels of myostatin in males: Implications for body composition

• DOI: 10.1016/j.molmet.2022.101464
• Publication Date: 2022-02-24T03:18:30Z
• Authors: Kate Lee; Sanaz Vakili; Hannah J. Burden; Shannon Adams; Greg C. Smith; Braydon Kulatea; Morag Wright-McNa...; Danielle Sword; Conor Watene-O’Su...; Robert D. Atiola; Ryan G. Paul; Lindsay D. Plank; Prasanna Kallingappa; Frances King; Phillip Wilcox; Tony R. Merriman; Jeremy D. Krebs; Rosemary M. Hall; Rinki Murphy; Troy L. Merry; Peter R. Shepherd
• Keywords: Myostatin; Minor allele frequency

The minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples Pacific islands (including New Zealand Māori and Polynesia), with a frequency up 25% these populations. This associates large increase body mass index (BMI) but significantly lower risk type-2 diabetes (T2D). It remains unclear whether increased BMI driven by adiposity or lean mass. We undertook composition analysis using DXA 189 young men descent living Aotearoa Zealand. Further investigation was carried out two orthologous Arg458Gln knockin mouse models on FVB/NJ C57BL/6j backgrounds. A associated fat when adjusted for (p < 0.05) circulating levels muscle inhibitory hormone myostatin 0.05). Supporting human data, significant reductions adipose tissue were observed mice. more older mice both backgrounds appeared be result reduced age-associated increases male background also had grip strength 0.01) Overall, results prove that A-allele reduction which likely contribute an age-dependent lowering mass, at least males.