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Circulating oxytocin is genetically determined and associated with obesity and impaired glucose tolerance

, , , , , , and . J. Clin. Endocrinol. Metab., 104 (11): 5621--5632 (November 2019)

Abstract

CONTEXT: 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. OBJECTIVES AND DESIGN: Here, we measured OXT in a study cohort (n = 721; 396 women, 325 men; mean age $\pm$ SD, 47.7 $\pm$ 15.2 years) with subphenotypes related to obesity, including anthropometric traits such as body mass index BMI (mean $\pm$ SD), 26.8 $\pm$ 4.6 kg/m2, waist-to-hip ratio (WHR; 0.88 $\pm$ 0.09), blood parameters (glucose, 5.32 $\pm$ 0.50 mmol/L; insulin, 5.3 $\pm$ 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. RESULTS: 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 30 kg/m2 (n = 137; 106.4 pg/mL, P = 8 $\times$ 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 $\times$ 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 $\times$ 10-8, explained variance 3\%). CONCLUSIONS: Our data show that OXT is genetically affected by a variant near OXT and is associated with obesity and impaired glucose tolerance.

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