Distribution of Variants and Identification of Novel Variants in Patients with Obesity Using Next-Generation Sequencing in Genes Associated with Obesity: A Single-Center Experience in Turkey

Abstract

Background: Obesity has become a common public health problem all over the world today. In recent years, studies on the genetic etiology of obesity have gained importance. As a result of these studies, 127 obesity-related loci have been identified. Objectives: The aim of this work was to screen obesity-related genes and review the literature. Methods: In this retrospective study, 41 obesity-related genes were screened in 116 patients by next-generation sequencing. These genes are DYRK1B, LEP, LEPR, MC4R, NR0B2, POMC, UCP3, ADRB2, ADRB3, AGRP, MC3R, NTRK2, PCSK1, SIM1, CARTPT, ENPP1, PPARG, PPARGC1B, PYY, SDC3, UCP1, ADIPOQ, PBEF (NAMP), ADN (CFD), RETN, PGC1 (PPARGC1A), CCK, NPY, GLUT4 (SLC2A4), ADD1, SREBP1 (SREBF1), PTP1B (PTPN1), IRS-1, GHRL, BDNF, NEGR1, SH2B1, GIPR, TMEM18, FTO, and SLC22A1. Results: Seventy-six of our patients were female, and 40 were male. As a result, 43 variants were detected in 39 (34.4%) patients. Of these, GHRL c.152G>A, MC4R c.496G>A, SH2B1 c.2083G>A, GIPR c.548G>A, ADIPOQ c.268G>A, and BDNF c.5C>T variants have been previously reported in the literature. In addition to the aforementioned variants, there are 37 novel variants that have not been previously reported. Among these, we classified the UCP3 c.126 + 1G>T variant as “Pathogenic” according to the American College of Medical Genetics and Genomics (ACMG) criteria. Four of 37 novel variants, respectively, ADRB2 c.1160_1163delTTGT (p.Phe387Trp*55), MC4R c.895C>T (p.Pro299Ser), POMC c.304C>T (p.Gln102*), and NR0B2 c.265C>T (p.Gln89*), were classified as “Likely Pathogenic.” A total of 32 novel variants among 37 novel variants were categorized as variants of uncertain significance. Conclusions: Understanding the genetics of obesity is an essential step toward treating and preventing this disease, which has become a global health problem. With this study, we wanted to contribute to the literature by reporting previously reported and novel variants we detected in our patients with obesity.