血清磷酸盐、BMI 和中老年人体成分：一项横断面关联分析和双向孟德尔随机化研究。
Serum Phosphate, BMI, and Body Composition of Middle-Aged and Older Adults: A Cross-Sectional Association Analysis and Bidirectional Mendelian Randomization Study.
机构信息
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
出版信息
J Nutr. 2022 Jan 11;152(1):276-285. doi: 10.1093/jn/nxab351.
BACKGROUND
Observational studies have reported associations between serum phosphate and BMI in specific clinical settings, but the nature of this relation in the general population is unclear.
OBJECTIVES
The aim of this study was twofold: to investigate the association between serum phosphate and BMI and body composition, as well as to explore evidence of causality through a bidirectional one-sample Mendelian randomization (MR) in the population-based Rotterdam Study (RS).
METHODS
Observational associations between phosphate (mg/dL) and BMI, lean mass, and fat percentage (fat%), estimated by DXA, were analyzed using multivariable regression models in 9202 participants aged 45-100 y from 3 RS cohorts. The role of serum leptin was examined in a subgroup of 1089 participants. For MR analyses, allele scores with 6 single-nucleotide polymorphisms (SNPs) for phosphate and 905 SNPs for BMI were constructed in 7983 participants.
RESULTS
Phosphate was inversely associated with BMI in the total population (β: -0.89; 95% CI: -1.17, -0.62), and stronger in women (β: -1.92; 95% CI: -2.20, -1.65) than in men (β: -0.37; 95% CI: -0.68, -0.06) (P-interaction < 0.05). Adjustment for leptin did not change results in men. In women, adjustment for leptin attenuated the association, but it was not abolished (β: -0.94; 95% CI: -1.45, -0.42). Phosphate was inversely associated with fat%, but not with lean mass, in both sexes. MR analyses suggested a causal effect of BMI on serum phosphate (β: -0.01; 95% CI: -0.02, 0.00) but not vice versa.
CONCLUSIONS
Serum phosphate was inversely associated with BMI and fat% in a population-based study of middle-aged and older adults, with a stronger effect in women than in men. Adjusting for leptin attenuated this relation in women only. MR results suggest a causal effect of BMI on phosphate but not vice versa. An underlying sex dimorphism in phosphate homeostasis should be further explored.
背景
观察性研究报告了血清磷酸盐与特定临床环境下 BMI 之间的关联，但在一般人群中这种关系的性质尚不清楚。
目的
本研究的目的有两个：一是探讨血清磷酸盐与 BMI 和身体成分之间的关系；二是通过在基于人群的鹿特丹研究（RS）中进行双向单样本孟德尔随机化（MR）来探索因果关系的证据。
方法
使用多变量回归模型分析了来自 RS 的 3 个队列中的 9202 名年龄在 45-100 岁的参与者的血清磷酸盐（mg/dL）与 BMI、瘦体重和脂肪百分比（脂肪%）之间的观察性关联。在 1089 名参与者的亚组中检查了血清瘦素的作用。对于 MR 分析，在 7983 名参与者中构建了 6 个单核苷酸多态性（SNP）用于磷酸盐的等位基因评分和 905 个用于 BMI 的 SNP。
结果
磷酸盐在总人口中与 BMI 呈负相关（β：-0.89；95%CI：-1.17，-0.62），在女性中比男性更强（β：-1.92；95%CI：-2.20，-1.65）（P 交互 < 0.05）。调整瘦素后，男性的结果并未改变。在女性中，调整瘦素后，关联减弱，但并未消除（β：-0.94；95%CI：-1.45，-0.42）。磷酸盐与男女两性的脂肪%呈负相关，但与瘦体重无关。MR 分析表明 BMI 对血清磷酸盐有因果影响（β：-0.01；95%CI：-0.02，0.00），但反之则不然。
结论
在一项针对中年和老年人的基于人群的研究中，血清磷酸盐与 BMI 和脂肪%呈负相关，女性的影响比男性更强。仅在女性中，调整瘦素后，这种关系减弱。MR 结果表明，BMI 对磷酸盐有因果影响，但反之则不然。应进一步探讨磷酸盐稳态中潜在的性别二态性。
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