Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany.
J Clin Endocrinol Metab. 2019 Nov 1;104(11):5621-5632. doi: 10.1210/jc.2019-00643.
Despite the emerging evidence on the role of oxytocin (OXT) in metabolic diseases, there is a lack of well-powered studies addressing the relationship of circulating OXT with obesity and diabetes.
Here, we measured OXT in a study cohort (n = 721; 396 women, 325 men; mean age ± SD, 47.7 ± 15.2 years) with subphenotypes related to obesity, including anthropometric traits such as body mass index [BMI (mean ± SD), 26.8 ± 4.6 kg/m2], waist-to-hip ratio (WHR; 0.88 ± 0.09), blood parameters (glucose, 5.32 ± 0.50 mmol/L; insulin, 5.3 ± 3.3 µU/mL), and oral glucose tolerance test to clarify the association with OXT. We also tested in a genome-wide association study (GWAS) whether the interindividual variation in OXT serum levels might be explained by genetic variation.
The OXT concentration was increased in subjects with elevated BMI and positively correlated with WHR, waist circumference, and triglyceride levels. The OXT concentration in subjects with BMI <25 kg/m2 was significantly lower (n = 256; 78.6 pg/mL) than in subjects with a BMI between 25 and 30 kg/m2 (n = 314; 98.5 pg/mL, P = 6 × 10-6) and with BMI >30 kg/m2 (n = 137; 106.4 pg/mL, P = 8 × 10-6). OXT levels were also positively correlated with plasma glucose and insulin and were elevated in subjects with impaired glucose tolerance (P = 4.6 × 10-3). Heritability of OXT was estimated at 12.8%. In a GWAS, two hits in linkage disequilibrium close (19 kb) to the OXT reached genome-wide significant association (top-hit rs12625893, P = 3.1 × 10-8, explained variance 3%).
Our data show that OXT is genetically affected by a variant near OXT and is associated with obesity and impaired glucose tolerance.
尽管催产素（OXT）在代谢性疾病中的作用的证据不断涌现，但针对循环 OXT 与肥胖和糖尿病之间关系的研究还缺乏充分的研究。
在这里，我们在一个研究队列中测量了 OXT（n = 721；396 名女性，325 名男性；平均年龄 ± SD，47.7 ± 15.2 岁），该队列具有与肥胖相关的亚表型，包括人体测量特征，如体重指数[BMI（平均值 ± SD），26.8 ± 4.6 kg/m2]，腰臀比（WHR；0.88 ± 0.09），血液参数（血糖，5.32 ± 0.50 mmol/L；胰岛素，5.3 ± 3.3 µU/mL），以及口服葡萄糖耐量试验，以阐明与 OXT 的关联。我们还在全基因组关联研究（GWAS）中测试了个体间 OXT 血清水平的差异是否可以用遗传变异来解释。
在 BMI 升高的受试者中，OXT 浓度升高，与 WHR、腰围和甘油三酯水平呈正相关。BMI<25 kg/m2 的受试者的 OXT 浓度明显低于 BMI 为 25-30 kg/m2 的受试者（n = 314；98.5 pg/mL，P = 6×10-6）和 BMI>30 kg/m2 的受试者（n = 137；106.4 pg/mL，P = 8×10-6）。OXT 水平与血浆葡萄糖和胰岛素呈正相关，在糖耐量受损的受试者中升高（P = 4.6×10-3）。OXT 的遗传度估计为 12.8%。在 GWAS 中，与 OXT 紧密连锁（19 kb）的两个位点达到全基因组显著关联（最强关联 rs12625893，P = 3.1×10-8，解释方差 3%）。
我们的数据表明，OXT 受 OXT 附近的变异体遗传影响，并与肥胖和糖耐量受损有关。
