De Novo BETA-2 adrenergic receptor gene variant associated with obesity
Authors: Yaman Kalender Derya Sema , Ertürk Mehmet Sercan , Subaşıoğlu Aslı , Gasımlı Roya , Örük Güzide Gonca , Gölbaşı Murat , Önder Pamuk Barış 
Published: January 2023

Introduction

Obesity is a known condition when the energy taken is more than the energy consumed. According to the World Obesity Atlas data, 1 out of every five women and 1 out of every seven men will live with obesity by 2030.The prevalence of obesity was 21.1% in Turkey (2019). Although environmental factors and changes in dietary patterns are essential in this increase, genetic factors also have an effect. Mutations in genes that affect catecholamine function, which play an essential role in energy consumption and lipolysis, also lead to obesity. One of these critical genes is the β2-adrenergic receptor gene (ADRB2). It was previously reported that it is responsible for regulating lipolysis and thermogenesis and is mainly expressed in the adipose tissues. This gene induces catecholamine activation and leads to lipid mobilization in adipose tissue.

Clinical Case

A 25-year-old male patient applied to our outpatient clinic with obesity, sexual dysfunction. The patient had been overweight since childhood and did not use any medication at admission. On physical examination, his body mass index:50.8 kg/cm2.and has only hair on the genital area and axilla. His parents are consanguineous, and his mother, father, and brother are also obese. He had diabetes mellitus, hypolipidemia, hypogonadotropic hypogonadism, and GH deficiency in his initial tests (Table-1). The other pituitary hormones were usual. There was not any pathology in the pituitary and brain magnetic resonance images. LHRH test result was interpreted as hypothalamic dysfunction. The insulin hypoglycemia test was performed due to growth hormone deficiency to accurate to GH deficiency. Clinic exome sequencing was performed on the patient, and a de novo heterozygous mutation in the ADRB2 gene was detected, which has a role in lipolysis, and thermogenesis and hence is important for obesity. Two more mutations were identified that related to thyroid functions. The DUOX2 gene variant has an association with thyroid dyshormonogenesis, and the IRS4 gene variant has a role in hypothyroidism. Further studies are needed to identify the pathogenicity of variants. Molecular identification of mutations has important implications for personalized medicine, including genetic counseling and the development of specific treatment protocols. We started the patient with exenatide 10 mg/day, metformin 2000 mg/day, testosterone propionate, and a diet program.

Conclusion

Studies show that low ADRB2 expression increases the risk of obesity. Obesity is increasing rapidly over time globally, and it is necessary to know the underlying pathophysiologies and genetic etiologies and to develop new treatment algorithms for this in order to reduce mortality and morbidity. Therefore, gene mutations underlying obesity, the metabolic changes it causes, environmental factors, and diet should be considered. Considering the scarcity of available anti-obesity drugs, understanding the genetic makeup may be influential in developing new therapeutic targets.