Research Article Prediction and Structural Comparison of Deleterious Coding Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) in Human LEP Gene Associated with Obesity Hind Bouafi, 1,2 Sara Bencheikh, 1 AL Mehdi Krami, 1 Imane Morjane, 1 Hicham Charoute, 1 Hassan Rouba, 1 Rachid Saile , 2 Fouad Benhnini, 3 and Abdelhamid Barakat 1 1 Laboratoire de Génomique et Génétique Humaine, Institut Pasteur du Maroc, Casablanca, Morocco 2 Laboratoire Biologie et Santé, Centre de Recherche Santé et Biotechnologie, Faculté des Sciences Ben M’Sik, Hassan II University of Casablanca, Morocco 3 Laboratoire de Signalisation cellulaire, Faculté des Sciences Meknès, Université Moulay Ismail, Morocco Correspondence should be addressed to Abdelhamid Barakat; hamid.barakat@pasteur.ma Received 14 May 2019; Revised 25 July 2019; Accepted 14 August 2019; Published 4 December 2019 Academic Editor: Betti Giusti Copyright © 2019 Hind Bouafi et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Leptin is a peptide hormone that regulates fat stores in the body and appetite by controlling the feeling of satiety. is hormone is secreted by the white adipose tissue and plays a role in the storage and mobilization of fatty acids. Mutations of the LEP gene have been associated with obesity in different populations; it is a multifactorial disease that constitutes a major public health problem. In this study, we evaluated the impact of missense SNPs in the LEP gene extracted from dbSNP using 8 computational prediction tools. Out of the total of 4337 SNPs, 93 were nsSNPs (nonsynonymous single nucleotide polymorphisms). Among 93 nsSNPs, 12 (S46L, G59S, D61N, D100N, N103K, C117S, D76V, S88C, P90R, I95N, L161R, and R105W) variants were predicted to be the most deleterious by prediction soſtware. On these 12 deleterious SNPs, 8 variants (S46L, G59S, D61N, D100N, N103K, C117S, L161R, and R105W) were located in the conserved positions and showed a decrease in structure stability which was evaluated by I-Mutant and Mupro. en, by analyzing the different interactions between different amino acids in wild and mutated proteins, we assessed the structural impact of the deleterious modifications using the YASARA soſtware. Among 8 deleterious nsSNPs, we revealed structure changes in the 6 variants S46L, G59S, D100N, L103K, R105W, L161R, two of which R105W, N103K were previously reported as associated with obesity. Our study suggests 6 deleterious mutations could play an important role in contributing to human obesity and worth to be included in association and functional studies, then may be a drug target. 1. Introduction Metabolic syndrome (MetS) is a worldwide epidemic complex disorder determined by a cluster of interconnected factors, which are dyslipidemia, hypertension, and dysregulated glu- cose homeostasis, while abdominal obesity and/or insulin resistance (IR) are the main manifestations of the syndrome. All of these factors increase the risk of cardiovascular athero- sclerotic diseases and type 2 diabetes mellitus [1]. Most of the epidemiological studies show that MetS’s prevalence ranges between 20% and 45% of the population [2]. Abdominal obesity has indeed recently gained increasing and special attention as the most prevalent manifestation of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) and the International Diabetes Federation (IDF) [3]. Moreover, in 2016, the number of overweight people reached as high as 1.9 billion adults worldwide of whom more than 650 million were obese [4]. e imbalance between caloric consumption and energy expenditure mainly characterizes obesity, which is defined, according to the World Health Organization by the calculation of the body mass index (BMI) determined by the following formula: weight in kilograms/height in meters 2, as well as by measuring waist circumference. Indeed, a BMI of 30 or more and a waist circumference greater than 80 cm in women and 94 cm in men indicate obesity [5]; furthermore, it becomes morbid when the BMI value exceeds 40 [4]. Hindawi BioMed Research International Volume 2019, Article ID 1832084, 10 pages https://doi.org/10.1155/2019/1832084