*Elwira Siewiec1, Urszula Puchta1, Lukasz Szczerbinski1, Anna Citko2, Hady Razak Hady3, Adam Jacek Kretowski1, 2
Genetics in obesity
Predyspozycje genetyczne rozwoju otyłości
1Department of Endocrinology, Diabetology and Internal Medicine, Faculty of Medicine, Medical University of Bialystok, Poland
2Clinical Research Center, Faculty of Medicine, Medical University of Bialystok, Poland
3Ist Department of General and Endocrinological Surgery, Faculty of Medicine, Medical University of Bialystok, Poland
Streszczenie
Otyłość jest jednym z najistotniejszych problemów współczesnej medycyny na całym świecie. Dotychczas uważano, iż rozwój otyłości jest ściśle uwarunkowany czynnikami środowiskowymi, jednak aktualne badania wykazały znaczenie genetycznych czynników w rozwoju choroby.
Praca poglądowa przedstawia aktualny stan wiedzy na temat genetycznych predyspozycji rozwoju otyłości. Przedyskutowano mono- i poligenową formę otyłości oraz podkreślono znaczenie badań asocjacyjnych całego genomu (GWAS), które dostarczają nowych informacji dotyczących patomechanizmu choroby.
Baza Pubmed została przeszukana pod względem artykułów odnoszących się do tematu podłoża genetycznego rozwoju otyłości, które ukazały się w latach 2005-2018.
Niezbędne jest dalsze pogłębianie wiedzy z zakresu genetyki otyłości, co pozwoli na zrozumienie mechanizmów molekularnych rozwoju choroby, która dotyczy milionów ludzi na całym świecie, jednocześnie pozwalając na rozwój nowoczesnych sposobów leczenia.
Summary
Obesity is one of the biggest problems of modern medicine. Recently it has evolved from epidemic to a global pandemic. Previously obesity was generally considered as a disease induced mostly by environmental factors but in recent years a lot of studies has shown that genetics may play important role in the development of the disease.
In this review we describe current knowledge of the genetics of obesity. We discuss monogenic forms of obesity, characterize polygenic or “common” obesity, and emphasize genome-wide association studies for obesity-related traits, which provided new insights into the genetics and physiology of obesity.
Pubmed was searched for articles relevant to genetic background of obesity published between 2005 and 2018. Some earlier applicable articles were also consulted.
Knowledge of obesity genetics has still to be explored, to enable an understanding the molecular mechanisms of a disorder that affects hundreds of millions of people, providing new advances in the management of a disease for which no effective treatment, apart from surgery, currently exists.
Introduction
The prevalence of overweight and obesity is escalating rapidly worldwide, emerging as one of the most serious public health challenges (1). Worldwide, roughly 40% of adults are overweight and 10-15% are obese (2). Overweight and obesity, respectively are associated with high risk of many chronic diseases, inclusive of type 2 diabetes, cancer, cardiovascular events (3, 4). The prodigious effort in the search to understand the physiological basis of obesity still needs to be taken.
Obesity emerges from the interactions between genetic profile and environmental risk factors. For instance, some of the “obesogenic environment” features are physical inactivity, excessive caloric intake, what results in an imbalance between energy intake and expenditure, and other such as medications, socioeconomic status, and feasibly novel factors like endocrine disruptors, the gastrointestinal microbiome or deficiency of sleep (5, 6). It is said that environmental factors are major causes of the obesity epidemic. The relative contribution between environmental aspects and genetic predisposition is still poorly understood. Wide interindividual discrepancy in body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) observed under comparable environmental conditions can only be ascribed to a genetic susceptibility to the condition. Therefore, obesity emerged as one of the most heritable human traits. However, this heritability can be inflected by various environmental factors (7). The comprehension of the genetic causes linked to obesity susceptibility may explain some of the underlying biology and may give rise to possible prevention and new treatments methods. Although, studies that involve twins and family subjects, have suggested that 40-70% of the interindividual discrepancy in obesity risk and BMI can refer to genetic factors, the exploration of obesity susceptibility loci has only recently started to be prosperous (8, 9).
Review
Monogenic obesity
Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Mam kod dostępu
- Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu albo wszystkich artykułów (w zależności od wybranej opcji), należy wprowadzić kod.
- Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.
- Aby kupić kod proszę skorzystać z jednej z poniższych opcji.
Opcja #1
29 zł
Wybieram
- dostęp do tego artykułu
- dostęp na 7 dni
uzyskany kod musi być wprowadzony na stronie artykułu, do którego został wykupiony
Opcja #2
69 zł
Wybieram
- dostęp do tego i pozostałych ponad 7000 artykułów
- dostęp na 30 dni
- najpopularniejsza opcja
Opcja #3
129 zł
Wybieram
- dostęp do tego i pozostałych ponad 7000 artykułów
- dostęp na 90 dni
- oszczędzasz 78 zł
Piśmiennictwo
1. Roberto CA, Swinburn B, Hawkes C et al.: Patchy progress on obesity prevention: emerging examples, entrenched barriers, and new thinking. Lancet 2015; 385: 2400-2409.
2. NCD Risk Factor Collaboration (NCD-RisC): Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 2016; 387: 1377-1396.
3. Kopelman P: Health risks associated with overweight and obesity. Obes Rev 2007; 8(1): 13-17.
4. Calle EE, Rodriguez C, Walker-Thurmond K et al.: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348(17): 1625-1638.
5. Maes HH, Neale MC, Eaves LJ: Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 1997; 27: 325-351.
6. French SA, Story M, Jeffery RW: Environmental influences on eating and physical activity. Annu Rev Public Health 2001; 22: 309-335.
7. El Sayed Moustafa JS, Froguel P: From obesity genetics to the future of personalized obesity therapy. Nat Rev Endocrinol 2013; 9: 402-413.
8. Stunkard AJ, Foch TT, Hrubec Z: A twin study of human obesity. JAMA 1986; 256: 51-54.
9. Day FR, Loos RJF: Developments in obesity genetics in the Era of Genome-Wide Association studies. J Nutrigenet Nutrigenomics 2011; 4: 222-238.
10. Walley AJ, Asher JE, Froguel P: The genetic contribution to non-syndromic human obesity. Nature Rev Genet 2009; 10: 431-442.
11. Oswal A, Yeo G: Leptin and the control of body weight: a review of its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity. Obesity (Silver Spring) 2010; 18: 221-229.
12. Clement K, Vaisse C, Lahlou N et al.: A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392(6674): 398-401.
13. Fischer-Posovszky P, von Schnurbein J, Moepps B et al.: A new missense mutation in the leptin gene causes mild obesity and hypogonadism without affecting T cell responsiveness. J Clin Endocrinol Metab 2010; 95(6): 2836-2840.
14. Cheung WW, Mao P: Recent advances in obesity: genetics and beyond. ISRN Endocrinol 2012; 2012: 536905.
15. Saeed S, Butt TA, Anwer M et al.: High prevalence of leptin and melanocortin-4 receptor gene mutations in children with severe obesity from Pakistani consanguineous families. Mol Genet Metab 2012; 106: 121-126.
16. Bell CG, Walley AJ, Froguel P: The genetics of human obesity. Nat Rev Genet 2005; 6: 221-234.
17. Farooqi IS, Keogh JM, Yeo G et al.: Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348: 1085-1095.
18. Krude H, Gruters A: Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome. Trends Endocrinol Metab 2000; 11: 15-22.
19. Locke AE, Kahali B, Berndt SI et al.: Genetic studies of body mass index yield new insights for obesity biology. Nature 2015; 518: 197-206.
20. Frayling TM, Timpson NJ, Weedon MN et al.: A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316: 889-894.
21. Pigeyre M, Yazadi FT, Kaur Y et al.: Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity. Clin Sci 2016; 130: 943-986.
22. Speliotes EK, Willer CJ, Berndt SI et al.: Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937-948.
23. Goodarzi MO: Genetics of obesity: what genetic association studies have taught us about the biology of obesity and its complications. Lancet Diabetes Endocrinol 2018; 6: 223-236.
24. Shungin D, Winkler TW, Croteau-Chonka DC et al.: New genetic loci link adipose and insulin biology to body fat distribution. Nature 2015; 518: 187-196.
25. Saeed S, Arslan M, Froguel P: Genetics of Obesity in Consanguineous Populations: Toward Precision Medicine and the Discovery of Novel Obesity Genes. Obesity 2018; 26(3): 474-484.