Genetic background in common forms of obesity – from studies on identical twins to candidate genes of obesity

Czech version

Authors: Běla Bendlová; Petra Lukášová; Markéta Vaňková; Daniela Vejražková; Olga Bradnová; Josef Včelák; Soňa Stanická; Hana Zamrazilová; Irena Aldhoon-Hainerová; Lenka Dušátková; Marie Kunešová; Vojtěch Hainer
Authors‘ workplace: Endokrinologický ústav, Praha
Published in: Čas. Lék. čes. 2014; 153: 193-199
Category: Review Articles

* Článek je věnovaný k 70. narozeninám doc. MUDr. Vojtěcha Hainera, CSc.

Overview

Common obesity is a result of interaction between genes and environmental/lifestyle factors, with heritability estimates 40–70%. Not only the susceptibility to obesity but also the success of weight management depends on the genetic background of each individual. This paper summarizes the up-to-date knowledge on genetic causes of common obesities. Introduction of genome-wide association studies (GWAS) led to an identification of a total of 32 variants associated with obesity/BMI and 14 with body fat distribution. Further, a great progress in revealing the mechanisms regulating the energy balance was also noted. However, the proportion of explained variance for BMI is still low, suggesting other mechanisms such as gene-gene and gene-environment interactions, rare gene variants, copy number variants polymorphisms, or epigenetic modifications and microRNAs regulating gene transcription. In summary, we present results of our studies on obesity risk variants in Czech adults, children and adolescents including those evaluating the influence of selected gene variants on the outcomes of weight management.

Keywords:
obesity – genome-wide association studies – candidate gene – single-nucleotide polymorphisms (SNPs) – BMI – anthropometric parameters – weight management – genotype-phenotype correlations

Sources

1. World Health Organization: Obesity and overweight, Fact sheet #311, May 2012.

2. Kelly T, et al. Global burdon of obesity in 2005 and projection to 2030. Int J Obes (Lond) 2008; 32: 1431–1437.

3. Serdula MK, et al. Do obese children become obese adults? A review of literature. Prev Med 1993; 22: 167–177.

4. Freedman DS, et al. Relation of body mass index and skinfold thickenesses to cardiovascular disease risk factors in children: the Bogalusa heart study. Am J Clin Nutr 2009; 90: 210–216.

5. Jansen I, et al. Prevalence and secular changes in abdominal obesity in Canadian adolescents and adults, 1981 to 2007–2009. Obes Rev 2011; 12: 397–405.

6. Jansen I, et al. Waist circumference and not body mass index explains obesity-related health risk. Ann J Clin Natur 2004; 79: 379–384.

7. Bigaard J, et al. Waist circumference and body composition in relation to all-cause mortality in middle-aged men and women. Int J Obes (Lond) 2005; 29: 778–784.

8. Erlichman J, et al. Physical activity and its impact on health outcomes. Paper 2: prevention of unhealthy weight gain and obesity by physical activity: and analysis of the evidence. Obes Rev 2002; 3: 273–287.

9. Stunkard AJ, et al. The body mass index of twins who have been reared apart. N Engl J Med 1990; 322: 1483–1487.

10. Allison DB et al. The heritability of body mass index among the international sample of monozygotic twins reared apart. Int J Obes Relat Met Disord 1996; 20: 501–506.

11. Maes HH, et al. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 1997; 27: 325–351.

12. Rankinen T, et al. The human obesity gene map: the 2005 update. Obesity (Silver Sring) 2006; 14: 529–644.

13. Sandholt CH, et al. Beyond the fourth wave of genome-wide obesity association studies. Nutr Diab 2012; 2: e37; doi:10.1038/nutd.2012.9.

14. Shmueli O, et al. GeneNote: whole genome expression profiles in normal human tissues. Comptes Rendus Biologies 2003; 326: 1067–1072.

15. van Vliet-Ostaptchouk JV, et al. Gene-lifestyle interactions in obesity. Curr Nutr Rep 2012; 1: 184–196.

16. Andreasen CH, et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 87: 95–101.

17. Hainer V, Kunesová M, Parízková J, et al. Serum cortisol and sex hormone binding globulin (SHBG) levels, body fat distribution and the role of genetic factors in obese females. Sb Lek. 2002; 103(4): 471–475.

18. Stich V, Harant I, De Glisezinski I, et al. Adipose tissue lipolysis and hormone-sensitive lipase expression during very-low-calorie diet in obese female identical twins. J Clin Endocrinol Metab 1997; 82(3): 739–744.

19. Kunesová M, Hainer V, Tvrzicka E, et al. Assessment of dietary and genetic factors influencing serum and adipose fatty acid composition in obese female identical twins. Lipids. 2002; 37(1): 27–32.

20. Fried M, Kasalicky M, Kunesova M, Hainer V. Influence of some hereditary factors on weight loss following conservative and surgical treatment of obese female monozygotic twins. Obes Surg. 1999; 9(3): 265–268.

21. Hainer V, Stunkard AJ, Kunesová M, et al. Intrapair resemblance in very low calorie diet-induced weight loss in female obese identical twins. Int J Obes Relat Metab Disord 2000; 24(8): 1051–1057.

22. Hainer V, Stunkard A, Kunesová M, et al. A twin study of weight loss and metabolic efficiency. Int J Obes Relat Metab Disord. 2001; 25(4): 533–537.

23. Hainer V, Kunešová M, Stunkard AJ, et al. The within-pair resemblance in serum levels of androgens, sex-hormone binding globulin and cortisol in female obese identical twins – effect of negative energy balance induced by very low-calorie diet. Horm Metab Res 2001; 33(7): 417–422.

24. Kunešová M, Phinney S, Hainer V, et al. The responses of serum and adipose Fatty acids to a one-year weight reduction regimen in female obese monozygotic twins. Ann N Y Acad Sci. 2002; 967: 311–323.

25. Bendlová B, Mazura I, Včelák J, et al. Is a mutation of the beta 3-adrenergic receptor gene related to non-insulin-dependent diabetes mellitus and juvenile hypertension in the Czech population? Ann N Y Acad Sci. 1997 20; 827: 135–143.

26. Bendlová B, Mazura I, Včelák J, et al. Mutation in the beta3-adrenergic receptor gene (Trp64Arg) does not influence insulin resistence, energy metabolism, fat distribution and lipid spectrum in young people. Pilot study. Vnitř. Lék. 1999; 45(5): 267–272.

27. Šrámková D, Kunešová M, Hainer V, et al. Is a Pro12Ala polymorphism of the PPARgamma2 gene related to obesity and type 2 diabetes mellitus in the Czech population? Ann N Y Acad Sci. 2002; 967: 265–273.

28. Bendlová B, et al. PPARgamma2 Pro12Ala polymorphism in relation to free fatty acids concentration and composition in lean healthy Czech individuals with and without family history of diabetes type 2. Physiol Res 2008; 57(Suppl 1): S77–90.

29. Šramková D, Krejbichová S, Včelák J, et al. The UCP1 gene polymorphism A-3826G in relation to DM2 and body composition in Czech population. Exp Clin Endocrinol Diabetes. 2007; 115(5): 303–307.

30. Včelák J, Lukášová P, Vaňková M, et al. FTO gene is associated not only with obesity-related quantitative traits but also wit higher OGTT stimulated glycaemia and leptin levels. Diabetologia 2008; 51(Suppl 1): A818: S326.

31. Wojciechowski P, Lipowska A, Rys P, et al. Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis. Diabetologia. 2012; 55(10): 2636–2645.

32. Hubáček JA, Bohuslavová R, Kuthanová L, et al. The FTO gene and obesity in a large Eastern European population sample: the HAPIEE study. Obesity (Silver Spring) 2008; 16(12): 2764–2766.

33. Hubáček JA, Piťha J, Adámková V, et al. A common variant in the FTO gene is associated with body mass index in males and postmenopausal females but not in premenopausal females. Czech post-MONICA and 3PMFs studies. Clin Chem Lab Med 2009; 47(4): 387–390.

34. Hubáček JA, Stanek V, Gebauerová M, et al. A FTO variant and risk of acute coronary syndrome. Clin Chim Acta 2010; 411(15–16): 1069–1072.

35. Hubáček JA, Viklický O, Dlouhá D, et al. The FTO gene polymorphism is associated with end-stage renal disease: two large independent case-control studies in a general population. Nephrol Dial Transplant 2012; 27(3): 1030–1035.

36. Dlouhá D, Piťha J, Lanská V, Hubáček JA. Association between FTO 1st intron tagging variant and telomere length in middle aged females. 3PMFs study. Clin Chim Acta 2012; 413(15–16):1222–1225.

37. Bradnová O., Vaňková M., Lukášová P., et al. Melanocortin-4 receptor gene polymorphism (rs12970134) influences glucose metabolism, leptin and GH levels in women. 12th European Congress of Endocrinology, 24.–28. 4. 2010, Prague, Czech Rep., Endocrine Abstracts 22: P352.

38. Lukášová P, Vaňková M, Včelák J, et al. Associations of Poly-morphisms in Several Common Obesity-Susceptibility Genes with Body-Mass Index and Other Anthropometric Characteristics. Diabetes 2011; 60(Suppl 1): A507: 1881.

39. Hainer V, Zamrazilová H, Spálová J, et al. Role of hereditary factors in weight loss and its maintenance. Physiol Res 2008; 57(Suppl 1): S1–15.

40. Aldhoon B, Zamrazilová H, Aldhoon Hainerová I, et al. Role of the PPARalpha Leu162Val and PPARgamma2 Pro12Ala gene polymorphisms in weight change after 2.5-year follow-up in Czech obese women. Folia Biol (Praha) 2010; 56(3): 116–123.

41. Spálová J, Zamrazilová H, Včelák J, et al. Neuromedin beta: P73T polymorphism in overweight and obese subjects. Physiol Res. 2008; 57(Suppl 1): S39–48.

42. Hainerová I, Torekov SS, Ek J, et al. Association between neuromedin U gene variants and overweight and obesity. J Clin Endocrinol Metab 2006; 91(12): 5057–5063.

43. Hainerová I, Larsen LH, Holst B, et al. Melanocortin 4 receptor mutations in obese Czech children: studies of prevalence, phenotype development, weight reduction response, and functional analysis. J Clin Endocrinol Metab 2007; 92(9): 3689–3696.

44. Hainerová I, Zamrazilová H, Sedláčková D, Hainer V. Hypogona-dotropic hypogonadism in a homozygous MC4R mutation carrier and the effect of sibutramine treatment on body weight and obesity-related health risks. Obes Facts 2011; 4(4): 324–328.

45. Dušátková L, Zamrazilová H, Sedláčková B, et al. Association of obesity susceptibility gene variants with metabolic syndrome and related traits in 1,443 czech adolescents. Folia Biol (Praha) 2013; 59(3): 123–133.

Labels

Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental Hygienist

MicroRNAs and kidneys

Monogenic obesity – current status of molecular genetic research and clinical importance

Article was published in

Journal of Czech Physicians

2014 Issue 4

Download issue PDF