Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Department of Anthropology, Yale University, New Haven, CT, USA.
Int J Obes (Lond). 2021 Jan;45(1):45-55. doi: 10.1038/s41366-020-00659-4. Epub 2020 Sep 3.
BACKGROUND/OBJECTIVES: In Samoa, where 80% of the adult population is living with obesity, understanding the determinants of adiposity and growth during infancy may inform prevention efforts. We examined the association of a missense variant, rs373863828, in the CREBRF gene with body composition in Samoan infants. Adults with one or more copies of the rs373863828 minor allele (A) have higher odds of obesity, based on body-mass index (BMI), but paradoxically decreased odds of diabetes compared to those without the allele. Our study may offer novel insight into the natural history and pathogenesis of this unexpected relationship.
SUBJECTS/METHODS: In a prospective study, we measured body composition in early infancy, and at 2- and 4-months of age using anthropometry and dual-energy x-ray absorptiometry (DXA). We genotyped subjects at the CREBRF rs373863828 locus and compared infants with (AA/AG) and without (GG) the variant. In longitudinal analyses, we calculated the absolute change in each outcome from the early infant to the 4-month assessment, adjusting for baseline and other covariates.
In cross-sectional analyses, there was no significant difference in infant BMI or fat mass by genotype. After adjusting for covariates, infants with the variant had 4.0 ± 1.8 g more bone mass (p = 0.026) and 210.9 ± 79.6 g more lean mass (p = 0.009) at 4-months and accumulated 176.9 ± 73.0 g more lean mass between the early infant and 4-month assessment (p = 0.017).
The CREBRF rs373863828 minor allele (A) was not associated with increased BMI or adiposity in Samoan infants, but instead with increased lean and bone mass. Our findings suggest that lean (i.e., muscle) and bone mass accretion should be explored as pathways to explain the "protective" effect of the CREBRF variant against diabetes.
背景/目的：在萨摩亚，80%的成年人口患有肥胖症，了解婴儿期肥胖和生长的决定因素可能有助于预防工作。我们研究了 CREBRF 基因中的错义变体 rs373863828 与萨摩亚婴儿的身体成分之间的关联。基于体重指数（BMI），携带 rs373863828 次要等位基因（A）的一个或多个副本的成年人肥胖的可能性更高，但与没有该等位基因的成年人相比，患糖尿病的可能性反而降低。我们的研究可能为这种意外关系的自然史和发病机制提供新的见解。
受试者/方法：在一项前瞻性研究中，我们使用人体测量学和双能 X 射线吸收法（DXA）在婴儿早期以及 2 个月和 4 个月大时测量身体成分。我们在 CREBRF rs373863828 基因座上对受试者进行基因分型，并比较了具有（AA/AG）和不具有（GG）变体的婴儿。在纵向分析中，我们从婴儿早期到 4 个月评估时计算每个结果的绝对变化，同时调整基线和其他协变量。
在横断面分析中，基因型与婴儿 BMI 或脂肪量之间没有显著差异。在调整了协变量后，具有变体的婴儿在 4 个月时的骨量增加了 4.0±1.8g（p=0.026），瘦体重增加了 210.9±79.6g（p=0.009），在婴儿早期和 4 个月评估之间累积增加了 176.9±73.0g 瘦体重（p=0.017）。
CREBRF rs373863828 次要等位基因（A）与萨摩亚婴儿 BMI 或肥胖的增加无关，但与瘦体重和骨量的增加有关。我们的发现表明，应探索瘦体重（即肌肉）和骨量的积累，作为解释 CREBRF 变异对糖尿病的“保护”作用的途径。
