Impact of Angiotensin II Type 1 Receptor Gene Polymorphism on Insulin Resistance in Polycystic Ovary Syndrome

H. El-Mesallamy; T. El-Refaie; R. A. El-Razek

doi:10.1055/s-0032-1333234

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2013; 121(04): 188-193
DOI: 10.1055/s-0032-1333234

Article

Impact of Angiotensin II Type 1 Receptor Gene Polymorphism on Insulin Resistance in Polycystic Ovary Syndrome

H. El-Mesallamy

¹Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo, Egypt

,

T. El-Refaie

²Obstetrics and Gynecology Department, Faculty of Medicine, Ain Shams University, Abassia, Cairo, Egypt

,

R. A. El-Razek

¹Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo, Egypt

› Author Affiliations

Abstract

Insulin resistance is allegedly a target pathophysiological mechanism in the pathogenesis of polycystic ovary syndrome. Moreover, this metabolic alteration is possibly genetically determined. In view of the recent evidence implicating genetic variants of the renin-angiotensin system as candidates in several metabolic disorders, we investigated the allele and genotype frequencies of the A1166 C polymorphism of the angiotensin II type 1 receptor in relation with various metabolic and biochemical parameters in affected females trying to asses its role in the pathogenesis of this syndrome. The study was conducted on 83 females of which 39 females served as the control group. The participants were matched for age, body mass index and degree of obesity. For all subjects biochemical parameters were assayed including soluble CD40 ligand together with fasting glucose and insulin which were used for calculation of insulin resistance indices, Genotyping performed using real time polymerase chain reaction revealed that the C allele frequency and the AC genotype were less frequently observed in patients compared to controls, however this difference was not statistically significant (p=0.146). Lack of the C allele was associated with adverse metabolic parameters including higher rate of insulin resistance as well as solubes CD40 ligand in the patients group. Results of the current study support a causative role for the A1166 C polymorphism of the angiotensin II type 1 gene polymorphism in the pathogenesis or phenotypic expression of polycystic ovary syndrome.

Key words

A1166C angiotensin II type 1 receptor gene polymorphism - real time polymerase chain reaction - insulin resistance indices - soluble CD40L

Full Text

References

References
1 Carmina E, Azziz R. Diagnosis, phenotype, and prevalence of polycystic ovary syndrome. Fertil Steril 2006; 86: JS7-JS8
2 Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med 2010; 8: 41
3 DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of IR in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril 2005; 83: 1454-1460
4 Galazis N, Iacovou C, Haoula Z et al. Metabolomic biomarkers of impaired glucose tolerance and type 2 diabetes mellitus with a potential for risk stratification in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2012; 160: 121-130
5 Schmidt J, Landin-Wilhelmsen K, Brännström M et al. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab 2011; 96: 3794-3803
6 Gonçalves PB, Ferreira R, Oliveira JF. Role of angiotensin in ovarian follicular development and ovulation in mammals: a review of recent advances. Reproduction 2012; 143: 11-20
7 Kalupahana NS, Moustaid-Moussa N. The renin-angiotensin system: a link between obesity, inflammation and IR. Obesity Reviews 2012; 13: 136-149
8 Dinh DH, Agruman F, Johnston CI et al. Angiotensin receptors: distribution, signalling and function. Clin Sci 2001; 100: 481-492
9 Akasaka H, Katsuya T, Saitoh S et al. Effects of angiotensin II type 1 receptor gene polymorphisms on IR in a Japanese general population: the Tanno-Sobetsu study. Hypertens Res 2006; 29: 961-967
10 Alavi-Shahri J, Behravan J, Hassany M et al. Association between angiotensin II type 1 receptor gene polymorphism and metabolic syndrome in a young female Iranian population. Arch Med Res 2010; 41: 343-349
11 Antoniades C, Bakogiannis C, Tousoulis D et al. The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J Am Col Cardiol 2009; 54: 669-677
12 Poggi M, Jager J, Paulmyer-Lacroix O. et al. The inflammatory receptor CD40 is expressed on human adipocytes: contribution to crosstalk between lymphocytes and adipocytes. Diabetologia 2009; 52: 1152-1163
13 Han SH, Koh KK, Quon MJ et al. The effects of simvastatin, losartan, and combined therapy on soluble CD40 ligand in hypercholesterolemic, hypertensive patients. Atherosclerosis 2007; 190: 205-211
14 Souza HP, Frediani D, Cobra AL et al. Angiotensin II modulates CD40 expression in vascular smooth muscle cells. Clin Sci 2009; 116: 423-431
15 The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Rep 2004; 19: 41-47
16 Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961; 21: 1440-1447
17 Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 1969; 6: 24-27
18 Richmond W. Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 1973; 19: 1350-1356
19 Katz A, Nambi SS, Mather K et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402-2410
20 Akbar SA, Khawaja NP, Brown PR et al. Angiotensin II type 1 and 2 receptors gene polymorphisms in pre-eclampsia and normal pregnancy in three different populations. Acta Obstetricia et Gynecologica 2009; 88: 606-611
21 Worobey C, Fisher ND, Cox D et al. Genetic polymorphisms and the risk of accelerated renal function decline in women. PLoS One 2009; 4: e4787
22 Sun J, Fan H, Che Y et al. Association between ACE gene I/D polymorphisms and hyperandrogenism in women with polycystic ovary syndrome (PCOS) and controls. BMC Med Genet 2009; 10: 64
23 Karabulut A, Turgut S, Turgut G. Angiotensin converting enzyme gene insertion/deletion polymorphism in patients with polycystic ovary syndrome. Gynecological Endocrinology 2010; 26: 393-398
24 Koika V, Georgopoulos NA, Piouka A et al. Increased frequency of the DI genotype of the Angiotensin-I Converting Enzyme (ACE) and association of the II genotype with IR in Polycystic Ovary Syndrome. Eur J Endocrinol 2012; 166: 695-702
25 Celik O, Sahin I, Celik N et al. Diagnostic potential of serum N-terminal pro-B-type brain natriuretic peptide level in detection of cardiac wall stress in women with polycystic ovary syndrome: a cross-sectional comparison study. Human Reproduction 2010; 22: 2992-2998
26 Cakal E, Ozkaya M, Engin-Ustun Y et al. Serum lipocalin-2 as an IR marker in patients with polycystic ovary syndrome. J Endocrinol Invest 2011; 34: 97-100
27 27 Marioli DJ, Koika V, Adonakis GL. et al. Armeni et al. No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia. Arch Gynecol Obstet 2010; 281: 1045-1049
28 Deng J, Chen M, Yang Q et al. Relation between IR and A1166C molecular variant of type 1 angiotensin II receptor gene in patients with coronary heart disease. Hua Xi Yi Ke Da Xue Xue Bao 2002; 33: 278-280
29 Abdollahi MR, Gaunt TR, Syddall HE et al. Angiotensin II type I receptor gene polymorphism: anthropometric and metabolic syndrome traits. J Med Genet 2005; 42: 396-401
30 Wang C, Li F, Takahashi N. The Renin Angiotensin System and the Metabolic Syndrome. The Open Hypertension Journal 2010; 3: 1-13
31 Harte A, McTernan P, Chetty R et al. Insulin-mediated upregulation of the renin angiotensin system in human subcutaneous adipocytes is reduced by rosiglitazone. Circulation 2005; 111: 1954-1961
32 Saitoh S. IR and rennin angiotensin aldosterone system. Nippon Rinsho 2009; 67: 729-734
33 Van Geel PP, Pinto YM, Buikema H et al. Is the A1166C polymorphism of the angiotensin II type 1 receptor involved in cardiovascular disease?. European Heart Journal 1998; 19: G13-G17
34 Wei Y, Sowers JR, Clark SE et al. Angiotensin II-induced skeletal muscle IR mediated by NF-kappaB activation via NADPH oxidase. Am J Physiol Endocrinol Metab 2008; 294: E345-E351
35 Oktem M, Ozcimen EE, Uckuyu A et al. Polycystic ovary syndrome is associated with elevated plasma soluble CD40 ligand, a marker of coronary artery disease. Fertil Steril 2009; 91: 2545-2550