Objective. Obesity is a complex heterogeneous disease that is caused by genes, environmental factors, and the interaction between the two. The leptin (LEP) and leptin receptor (LEPR) genes have been evaluated for polymorphisms that could potentially be related to the pathophysiology of obesity and its complications. The aim of this study was to investigate the role of LEP G2548A and LEPR 668A/G polymorphisms in the pathogenesis of obesity. Subjects. The study included 127 patients with obesity and 105 healthy controls. Polymerase chain reaction and restriction fragment length analysis for LEP G2548A and LEPR 668A/G polymorphisms were applied. Results. There was no statistically significant difference in the genotype frequencies of the LEP gene polymorphism between patients and control groups ( ). We found a difference in the LEPR genotypes between patients and controls, but this was not statistically significant ( ). Additionally, we found an increased risk of obesity in the LEP/LEPR GG/GG combined genotype ( ). Conclusion. Our findings indicate that the LEP G2548A polymorphism is not a relevant obesity marker and that the LEPR 668A/G polymorphism may be related to obesity in a Turkish population. Further researches with larger patient population are necessary to ascertain the implications of LEP and LEPR polymorphisms in obesity. 1. Introduction Obesity is a complex heterogeneous disease that is caused by genes, environmental factors, and the interaction between the two [1]. Obesity is also a multifactorial condition, and many endocrine and inflammatory pathways are involved in its development and in obesity-related diseases [2]. Excess weight in obesity may come from muscles, bone, fat, and/or body water, but obesity specifically refers to having an abnormally high proportion of total body fat [3]. The World Health Organization defines “overweight” as a body mass index (BMI) of 25 or more and “obesity” as a BMI of 30 or more [4]. The prevalence of obesity has been stated as being near epidemic size [1–3, 5–7], and obesity has been associated with type II diabetes, hypertension, coronary artery disease, stroke, and many forms of cancer [8, 9]. Therefore, it is important that the underlying pathophysiology of obesity-related diseases is understood. Obesity results from the combined effects of genes, lifestyle, and the interactions of these factors [10], and both familial and nonfamilial factors play an important role in its development [1]. A genetic predisposition to obesity has been reported as a major risk factor for individuals [7]. With the
References
[1]
A. Nirmala, B. M. Reddy, and P. P. Reddy, “Genetics of human obesity: an overview,” International Journal of Human Genetics, vol. 8, no. 1-2, pp. 217–226, 2008.
[2]
R. de Mutsert, M. den Heijer, T. J. Rabelink, et al., “The Netherlands Epidemiology of Obesity (NEO) study: study design and data collection,” European Journal of Epidemiology, vol. 28, no. 6, pp. 513–523, 2013.
[3]
A. K. Afridi and A. Khan, “Prevalence and etiology of obesity—an overview,” Pakistan Journal of Nutrition, vol. 3, no. 1, pp. 14–25, 2004.
[4]
S. F. Noria and T. Grantcharov, “Biological effects of bariatric surgery on obesity-related comorbidities,” Canadian Journal of Surgery, vol. 56, no. 1, pp. 47–57, 2013.
[5]
Y. S. Lee, “The role of genes in the current obesity epidemic,” Annals of the Academy of Medicine Singapore, vol. 38, no. 1, pp. 45–47, 2009.
[6]
B. Rokholm, C. S. Andersen, and T. I. A. S？rensen, “Developmental origins of obesity—genetic and epigenetic determinants,” The Open Obesity Journal, vol. 3, pp. 27–33, 2011.
[7]
L. Brunkwall, U. Ericson, S. Hellstrand, B. Gullberg, M. Orho-Melander, and E. Sonestedt, “Genetic variation in the fat mass and obesity-associated gene (FTO) in association with food preferences in healthy adults,” Food & Nutrition Research, vol. 12, p. 57, 2013.
[8]
N. S. Wellman and B. Friedberg, “Causes and consequences of adult obesity: health, social and economic impacts in the United States,” Asia Pacific Journal of Clinical Nutrition, vol. 11, supplement 8, pp. S705–S709, 2002.
[9]
C. G. Bell, A. J. Walley, and P. Froguel, “The genetics of human obesity,” Nature Reviews Genetics, vol. 6, no. 3, pp. 221–234, 2005.
[10]
S. F. Pimentel Duarte, E. A. Francischetti, V. Genelhu-Abreu et al., “p.Q223R leptin receptor polymorphism associated with obesity in Brazilian multiethnic subjects,” American Journal of Human Biology, vol. 18, no. 4, pp. 448–453, 2006.
[11]
S. F. P. Duarte, E. A. Francischetti, V. A. Genelhu, P. H. Cabello, and M. M. G. Pimentel, “LEPR p.Q223R, β3-AR p.W64R and LEP c.-2548G>A gene variants in obese Brazilian subjects,” Genetics and Molecular Research, vol. 6, no. 4, pp. 1035–1043, 2007.
[12]
I. Bircan, “Genetics of obesity,” Journal of Clinical Research in Pediatric Endocrinology, supplement 1, pp. 54–57, 2009.
[13]
A. Nieters, N. Becker, and J. Linseisen, “Polymorphisms in candidate obesity genes and their interaction with dietary intake of n-6 polyunsaturated fatty acids affect obesity risk in a sub-sample of the EPIC-Heidelberg cohort,” European Journal of Nutrition, vol. 41, no. 5, pp. 210–221, 2002.
[14]
O. Portolés, J. V. Sorlí, F. Francés, et al., “Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain,” European Journal of Epidemiology, vol. 21, no. 8, pp. 605–612, 2006.
[15]
A. Constantin, G. Costache, A. V. Sima, C. S. Glavce, M. Vladica, and D. L. Popov, “Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects,” Biochemical and Biophysical Research Communications, vol. 391, no. 1, pp. 282–286, 2010.
[16]
I. S. Farooqi and S. O'Rahilly, “Genetic factors in human obesity,” Obesity Reviews, vol. 8, no. 1, pp. 37–40, 2007.
[17]
R. J. F. Loos, “Recent progress in the genetics of common obesity,” British Journal of Clinical Pharmacology, vol. 68, no. 6, pp. 811–829, 2009.
[18]
J. Hoffstedt, P. Eriksson, S. Mottagui-Tabar, and P. Arner, “A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin,” Hormone and Metabolic Research, vol. 34, no. 7, pp. 355–359, 2002.
[19]
O. Mammès, D. Betoulle, R. Aubert, B. Herbeth, G. Siest, and F. Fumeron, “Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight,” Annals of Human Genetics, vol. 64, no. 5, pp. 391–394, 2000.
[20]
J. G. Gregoor, H. Mulder, D. Cohen et al., “Combined HTR2C-LEP genotype as a determinant of obesity in patients using antipsychotic medication,” Journal of Clinical Psychopharmacology, vol. 30, no. 6, pp. 702–705, 2010.
[21]
Z. Yu, S. Han, X. Cao, C. Zhu, X. Wang, and X. Guo, “Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis,” Obesity, vol. 20, no. 2, pp. 396–406, 2012.
[22]
Y. C. Chagnon, J. H. Wilmore, I. B. Borecki et al., “Associations between the leptin receptor gene and adiposity in middle-aged caucasian males from the HERITAGE family study,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 1, pp. 29–34, 2000.
[23]
N. Yiannakouris, M. Yannakoulia, L. Melistas, J. L. Chan, D. Klimis-Zacas, and C. S. Mantzoros, “The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 9, pp. 4434–4439, 2001.
[24]
V. S. Mattevi, V. M. Zembrzuski, and M. H. Hutz, “Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil,” International Journal of Obesity, vol. 26, no. 9, pp. 1179–1185, 2002.
[25]
I. Boumaiza, A. Omezzine, J. Rejeb, et al., “Relationship between leptin G2548A and leptin receptor Q223R gene polymorphisms and obesity and metabolic syndrome risk in Tunisian volunteers,” Genetic Testing and Molecular Biomarkers, vol. 16, no. 7, pp. 726–733, 2012.
[26]
H. M. Hinuy, M. H. Hirata, M. F. Sampaio et al., “Relationship between variants of the leptin gene and obesity and metabolic biomarkers in Brazilian individuals,” Arquivos Brasileiros de Endocrinologia e Metabologia, vol. 54, no. 3, pp. 282–288, 2010.
