INFLUENCE OF b2 ADRENERGIC RECEPTOR POLYMORPHISM (RS1042713 AND RS1042714) ON ANTHROPOMETRIC, HORMONAL AND LIPID PROFILES IN POLYCYSTIC OVARIAN SYNDROME

  • Maha H. Daghestani Department of Zoology, Center for Female Scientific and Medical Colleges, King Saud University, Saudi Arabia
  • Maha Omair Department of Statistics and Operations Research, College of Science, King Saud University, Saudi Arabia
  • Mazin Daghestani Department of Obstetrics & Gynecology, Umm-Al-Qura University, Saudi Arabia
  • Sonya S. Abdel-Razeq Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
  • Namik Kaya Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
  • Arjumand Warsy Senior Scientist, Central Laboratory, Center for Female Scientific and Medical Colleges, King Saud University, Saudi Arabia
Keywords: beta-adrenergic receptor, leptin, lipids, polycystic ovary syndrome, single nucleotide polymorphism

Abstract


Background: Polycystic ovarian syndrome (PCOS) is a frequently encountered disorder. This study aimed to identify polymorphisms in ADRB2 in Saudi PCOS development and to study its influence on lipids, hormones, and anthropometric parameters.
Methods: Saudi females (100) suffering from PCOS and healthy controls (100) were investigated. The estimation of cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), plasma glucose, leptin, insulin, and ghrelin were carried out. The DNA was extracted, and ADRB2 fragment carrying the exon 1 was amplified and sequenced.
Results: The waist, W/H ratio, lipids, glucose, and insulin were significantly higher in the obese PCOS compared to the normal weight group. The leptin and ghrelin were not different. Two single nucleotide polymorphisms (SNPs): rs1042713(Arg16Gly; A>G) and rs1042714 (Gln27Glu; C>G) were identified. The genotype and allele frequency of rs1042713 did not differ in the total PCOS and normal weight, and obese PCOS compare to the controls. However, rs1042714 was significantly associated with PCOS development, where the minor G allele was protective against PCOS development.
Conclusions: The rs1042714 polymorphism of the ADRB associates with PCOS development in Saudis, while rs1042713 does not. However, the GG genotype of rs1042713 associates significantly with elevated BMI, waist, hip, W/H, and leptin, and decreased ghrelin. On the other hand, rs1042714 genotypes do not associate with any abnormality except the homozygous GG have higher triglycerides and lower HDL-C. Interestingly, glucose showed different correlation patterns in individuals carrying different genotypes of the two studied SNP, indicating clearly that the metabolic responses to a normal nutrient are significantly influenced by the genotypes of the SNPs in ADRB2.

References

1. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clinical Epidemiology 2014; 6: 1–13.

2. Hart R. Definitions, prevalence and symptoms of polycystic ovaries and the polycystic ovary syndrome. In: Allahbadia GN, Agrawal R (Ed). Polycystic Ovary
Syndrome. Kent, UK: Anshan, Ltd 2007: 15–26.

3. Rosenfield RL. Clinical review: identifying children at risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92: 787–96.

4. Allahbadia GN, Agrawal R (Ed). Polycystic Ovary Syndrome. Kent, UK: Anshan, Ltd 2007: 157–63.

5. Nasser AH, Ezz AZN, Abdel-Mageed MH, Radwan AR. Body mass index and c-reactive protein are potential predictors of asthma development in Egyptian polycystic ovary syndrome patients. J Med Biochem 2019; 38: 427–36.

6. Kurabayashi T, Yahata T, Quan J, Tanaka K. Association of polymorphisms in the beta2 and beta3 adrenoceptor gene with polycystic ovary syndrome. J Reprod Med 2006; 51: 389–93.

7. Tellechea ML, Muzzio DO, Iglesias Molli AE, Belli SH, Graffigna MN, Levalle OA, et al. Association between 2-adrenoceptor (ADRB2) haplotypes and insulin resistance in PCOS. Clin Endocrinol (Oxf) 2013; 78: 600–6.

8. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19–25.

9. Alshammari G, Khan R, Brameld J, Amer S, Lomax MA. Gene expression of inflammatory markers in adipose tissue between obese women with polycystic ovary and normal obese women. Eur Rev Med Pharmacol Sci 2017; 21: 1099–105.

10. Coskun S, Otu HH, Awartani KA, Al-Alwan LA, AlHassan S, Al-Mayman H, et al. Gene expression profiling of granulosa cells from PCOS patients following varying doses of human chorionic gonadotropin. J Assist Reprod Genet 2013; 30: 341–52.

11. Daghestani MH, Daghestani MH, El-Mazny A. Circulating ghrelin levels and the polycystic ovary syndrome: correlation with the clinical, hormonal and metabolic features. Eur J Obstet Gynecol Reprod Biol 2011; 155: 65–8.

12. Masuo K, Katsuya T, Fu Y, Rakugi H, Ogihara T, Tuck ML. 2- and 3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years. Circulation 2005; 111(25): 3429– 434. [PubMed] [Google Scholar].

13. González Sánchez JL, Proenza AM, Martínez Larrad MT, et al. The glutamine 27 glutamic acid polymorphism of the 2-adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population-based study in Spain. Clinical Endocrinology 2003; 59(4): 476–481.

14. Masuo K, Katsuya T, Fu Y, Rakugi H, Ogihara T, Tuck ML. 2-adrenoceptor polymorphisms relate to insulin resistance and sympathetic overactivity as early markers of metabolic disease in nonobese, normotensive individuals. American Journal of Hypertension 2005; 18(7): 1009–1014.

15. Daghestani MH, Warsy A, Daghestani MH, Al-Odaib AN, Eldali A, Al-Eisa NA,Omer SA, Hassan ZK. Arginine 16 Glycine Polymorphism in 2-Adrenergic Receptor Gene is Associated with Obesity, Hyperlipidemia, Hyper leptinemia, and Insulin Resistance in Saudis. Int J Endocrinol. 2012; 2012: 945608. doi: 10.1155/2012/945608. Epub 2012 Sep 27. PubMed PMID: 23056045; PubMed CentralPMCID: PMC3463944.

16. Daghestani MH, Warsy A, Daghestani MH, Al-odaib AN, Eldali A, Al-Eisa NA, Al-zhrani S. The Gln27Glu polymorphism in 2-adrenergic receptor gene is linked to hypertriglyceridemia, hyperinsulinemia and hyperleptinemia in Saudis. Lipids Health Dis. 2010 Aug 25; 9: 90. doi: 10.1186/1476-511X-9-90. PubMed PMID: 20738880; PubMed Central PMCID: PMC2940865.

17. Fenech A, Hall IP: Pharmacogenetics of asthma. J Clin Pharmacol 2002, 53: 3-15. 10.1046/j.0306-5251. 2001.01509.x.

18. Kaye, SA, Folsom AR, Prineas RJ, Potter JD, Gapstur SM. The Association of Body Fat Distribution with Lifestyle and Reproductive Factors in a Population Study of Post menopausal Women. Int J Obes 1990; 14: 583–591.

19. Hollmann M, Runnebam B, Gerhard I. Impact of waist –hip ratio and body mass index on hormonal and metabolic parameters in young obese women. Int J Obes 1997; 21: 476–83.

20. Landin K, Krotkiewski M, Smith U. Importance of obesity for the metabolic abnormalities associated with an abdominal fat distribution. Metabolism 1989; 38: 572–6.

21. Pirwany IR,Fleming R,Greer IA,Packard CJ, Sattar N. Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters. Clin Endocrinol (Oxf) 2001; 54: 447–53.

22. Luo X, Xu L. Association of fat distribution with metabolic syndrome in patients with polycystic ovary syndrome. Nan Fang Yi Ke Da Xue Xue Bao 2012; 32: 1325–7.

23. Bodenant M, Kuulasmaa K, Wagner A, et al. Measures of abdominal adiposity and the risk of stroke: the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) study, Stroke 2011: 42; 2872–7.

24. Kim JJ, Choi YM, Cho YM, Jung HS, Chae SJ, Hwang KR, et al. Prevalence of elevated glycated hemoglobin in women with polycystic ovary syndrome. Hum Reprod 2012; 27: 1439–44.

25. Palmert MR, Gordon CM, Kartashov AI, Legro RS, Emans SJ, Dunaif A. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 1017–23.

26. Wei D, Zhang B, Shi Y, Zhang L, Zhao S, Du Y et al. Effect of Preconception Impaired Glucose Tolerance on Pregnancy Outcomes in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2017; 102: 3822–9.

27. Csenteri OK, Sándor J, Kalina E, Bhattoa HP, G dény S. The role of hyperinsulinemia as a cardiometabolic risk factor independent of obesity in polycystic ovary syndrome. Gynecol Endocrinol 2017; 33: 34–8.

28. Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab 2005; 90: 3236–42.

29. Xu L, Yue L, Tan S, Yang S, Qiu D, Kong Y et al. [Polycystic ovarian syndrome and hyperinsulinemia]. Hua Xi Yi Ke Da Xue Xue Bao 2001; 32: 303–6.

30. Csenteri OK, Sándor J, Kalina E, Bhattoa HP, G dény S. The role of hyperinsulinemia as a cardiometabolic risk factor independent of obesity in polycystic ovary syndrome. Gynecol Endocrinol 2017; 33: 34–8.

31. Zheng SH, Du DF, Li XL. Leptin Levels in Women with Polycystic Ovary Syndrome: A Systematic Review and a Meta-Analysis. Reprod Sci 2017; 24: 656–70.

32. Kedikova SE, Sirakov MM, Boyadzhieva MV. Leptin levels and adipose tissue percentage in adolescents with polycystic ovary syndrome. Gynecol Endocrinol 2013; 29: 384–7.

33. Gao T, Wu L, Chang F, Cao G. Low circulating ghrelin levels in women with polycystic ovary syndrome: a systematic review and meta-analysis. Endocr J 2016; 63: 93–100.

34. Kurabayashi T, Yahata T, Quan J, Tanaka K. Association of polymorphisms in the beta2 and beta3 adrenoceptor gene with polycystic ovary syndrome. J Reprod Med 2006; 51: 389–93.

35. Park HS, Shin ES, Lee JE. Genotypes and haplotypes of beta2-adrenergic receptor and parameters of the metabolic syndrome in Korean adolescents. Metabolism 2008; 57(8): 1064–70.

36. Isaza C, Henao J, Ramirez E, Cuesta F, Cacabelos R. Polymorphic variants of the beta2-adrenergic receptor (ADRB2) gene and ADRB2-related propanolol induced dyslipidemia in the Colombian population. Methods Find Exp Clin Pharmacol 2005; 27: 237–44.

37. Wu HM, Bai H, Fan P, Liu R, Liu Y, Liu BW. [Analysis of beta2-adrenergic receptor gene (beta2AR) Arg16Gly polymorphism in patients with endogenous hypertriglyceridemia in Chinese population]. Zhonghua Yi Xue Yi ChuanXueZaZhi 2008; 25: 50–4.

38. Rosmond R, Ukkola O, Chagnon M, Bouchard C, Björntorp P. Polymorphisms of the beta2-adrenergic receptor gene (ADRB2) in relation to cardiovascular risk
factors in men. J Intern Med 2000; 248: 239–44.

39. Ukkola O, Rankinen T, Weisnagel SJ, Sun G, Pérusse L, Chagnon YC et al. Interactions among the alpha2-, beta2-, and beta3-adrenergic receptor genes and obesity-related phenotypes in the Quebec Family Study. Metabolism 2000; 49: 1063–70.

40. Wolk R, Snyder EM, Somers VK, Turner ST, Olson LJ, Johnson BD. Arginine 16 glycine beta2-adrenoceptor polymorphism and cardiovascular structure and function in patients with heart failure. J Am Soc Echocardiogr 2007; 20: 290–7.

41. Vardeny O, Nicholas G, Andrei A, Buhr KA, Hermanson MP, Moran JJ et al. b-AR polymorphisms and glycemic and lipid parameters in hypertensive individuals receiving carvedilol or metoprolol. Am J Hypertens 2012; 25: 920–6.
Published
2020/04/16
Section
Original paper