Cogprints
Login | Create Account

Evaluation of endothelial and platelet functions with intergenotypic variation of eNOS Glu298Asp gene polymorphism in relation to postmenopausal women

Pradeep Kumar Dabla, Sarika Arora, Shubha Sagar Trivedi, Nibhriti Das, Jayashrees Bhattacharjee (2010) Evaluation of endothelial and platelet functions with intergenotypic variation of eNOS Glu298Asp gene polymorphism in relation to postmenopausal women. [Journal (Paginated)]

Full text available as:

[img]PDF (Evaluation of endothelial and platelet functions with intergenotypic variation of eNOS Glu298Asp gene polymorphism in relation to postmenopausal women) - Published Version
Available under License Creative Commons Attribution No Derivatives.
686Kb

Abstract

Menopause is associated with increased Coronary Artery Disease (CAD) risk. This study was planned to elucidate the endothelial changes and platelet dysfunction and intergenotypic variation of NO levels in eNOS Glu298Asp gene polymorphism in postmenopausal women. This study was done on 200 women in the age group 40-55 years were selected from a tertiary care hospital. Of these, 100 postmenopausal women were included in study group and 100 premenopausal women served as control. Fasting blood samples were evaluated for plasma estriol, Nitric Oxide (NO) and Platelet Factor-4 (PF-4) levels. PCR-RFLP was done in remaining cell aggregate to study eNOS Glu298Asp gene polymorphism. Statistical evaluation was done on SPSS. Postmenopausal women had significantly lower estriol and NO levels as compared to premenopausal women (p<0.001). Significant positive correlation was found between age with PF4 in study group (p<0.01) and NO with estriol in both groups whereas negative correlation was observed between NO with PF4 in both groups. Distribution of genotype GG, GT and TT in postmenopausal and premenopausal women was found to be 82, 18, 0% and 90, 10, 0% respectively. All genotypes (GG+GT, GG and GT) showed significant decrease (p<0.001) in NO level in postmenopausal women. Decreased estrogen levels in postmenopausal state lead to endothelial and platelet dysfunction due to low NO levels. Further presence of eNOS gene polymorphism may provide additional insult by decreasing NO levels adding to the CAD risk. Hence, postmenopausal women those who presents with eNOS Glu298Asp polymorphic gene may have higher CAD risk.

Item Type:Journal (Paginated)
Keywords:Postmenopausal Women, Estrogen, Nitric Oxide, Platelet Factor-4, eNOS Glu298Asp gene polymorphism
Subjects:JOURNALS
ID Code:7089
Deposited By:International Journal of Biological and Medical Research , (IJBMR) ISSN:0976-6685
Deposited On:26 Oct 2010 19:12
Last Modified:11 Mar 2011 08:57

References in Article

Select the SEEK icon to attempt to find the referenced article. If it does not appear to be in cogprints you will be forwarded to the paracite service. Poorly formated references will probably not work.

[1] Kannel WB. Metabolic risk factors for coronary heart disease in women: perspective from the Framingham Study. Am Heart J. 1987; 114(2): 413-419.

[2] Bush TL. The epidemiology of cardiovascular disease in postmenopausal women. Ann N Y Acad Sci. 1990; 592: 263-271.

[3] Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, Sacks FM. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. New Engl J Med. 1991; 325(17): 1l96-1204.

[4] Rifici VA, Khachadurian AK. The inhibition of low-density lipoprotein oxidation by 17-beta estradiol. Metabolism. 1992; 41(10): 1110-1114.

[5] Melino G, Bernassola F, Knight RA, Corasaniti MT, Nistico G, Finnazi-AgroA. S-nitrosylation regulates apoptosis. Nature. 1997; 388(6641); 432-433.

[6] Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem J.1994; 298: 249-258.

[7] Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol.1996; 271: 1424-1437.

[8] Haynes WG, Noon JP, Walker BR, Webb DJ. Inhibition of nitric oxide synthesis increases blood pressure in healthy humans. J Hypertens. 1993; 11(12): 1375-1380.

[9] De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MA Jr, Shin WS, Liao JK. Nitric oxide decreases cytokine induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest. 1995; 96(1): 60-68.

[10] Sarkar R, Meinberg EG, Stanley JC, Gordon D, Webb RC. Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. Circ Res. 1996; 78(2): 225-230.

[11] Srivastava K, Biswas UK, Narang R, Varghese JJ, Das N. Prevalence of eNOS Glu298Asp polymorphism in healthy volunteers from a region of northen India. Community Genet. 2005; 8: 180-183.

[12] Faxon DP, Fuster V, Libby P, Beckman JA, Hiatt WR, Thompson RW, Topper JN, Annex BH, Rundback JH, Fabunmi RP, Robertson RM, Loscalzo J. Atherosclerotic Vascular Disease Conference Writing Group III: Pathophysiology. Circulation. 2004; 109:2617–2625.

[13] Sander HJ, Slot JW, Bouma BN, Bolhuis PA, Pepper DS, Sixma JJ. Immunocytochemical localization of fibrinogen, platelet factor 4 and beta thromboglobulin in thin frozen sections of human blood platelets. J Clin Invest. 1983; 72 (4): 1277-1287.

[14] Mathew F, Glenda J, Jack L. Quantification of nitric and nitrate in extracellular fluids. Metho Enzymol. 1996; 268: 237-246.

[15] Vinning RF, McGinley R, Rice BV. Saliva estriol measurements- an alternative to the assay of serum unconjugated estriol in assessing feto-placental function. J Clin Endoc Metab. 1983; 56: 454.

[16] Files JC, Malpas TW, Harter LA. Studies of human platelet – a granule release in vivo. Blood. 1981; 10: 186-194.

[17] Hibi K, Ishigami T, Tamura K, Mizushima S, Watanabe Y, Yoshii Y, Kihara M, Kimura K, Ishii M, Umemura S.. Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction. Hypertension. 1998; 32: 521-526.

[18] Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acid Res. 1988; 16: 1215.

[19] Salhotra S, Arora S, Anubhuti, Trivedi SS, Bhattacharjee J. Influence of menopause on biochemical markers of endothelial - A case control pilot study in North Indian population. Maturitas. 2009; 62: 166–170

[20] Majumdar NG, Robson SC, Ford GA. Effects of the menopause, gender and estrogen replacement therapy on vascular nitric oxide activity. J Clin Endocrinol Metab. 2000; 85(4): 1577- 1583.

[21] Wellman GC, Bonev AD, Nelson MT, Brayden JE. Gender differences in coronary artery diameter involve estrogen, nitric oxide and calcium dependent potassium channels. Circ Res. 1996; 79(5): 1024-1030.

[22] Rahimian R, Chan L, Goel A, Poburko D, Breemen CV. Estrogen modulation of endothelium-derived relaxing factors by human endothelial cells. Biochem Biophys Res Commun. 2004; 322 (2): 373-379.

[23] Amant C, Holm P, Xu Sh , Tritman N, Lsordo DW. Estrogen receptor mediated, nitric oxide dependent modulation of the immunological barrier function of ebndothelium: regulation of Fas ligand expression by estradiol. Circulation. 2001; 104 (21): 2576-2581.

[24] MacRitchie AN, Jun SS, Chen ZG, , German Z, Yuhanna IS, Sherman TS, Shaul PW. Estrogen upregulates endothelial nitric oxide synthase gene expression in fetal pulmonary artery endothelium. Circ Res. 1997; 81:355–362.

[25] Kaplan KL, Nossel HL, Drillings M, Lesznik G. Radioimmunoassay of platelet factor 4 and β-thromboglubulin: development and application to studies of platelet release in relation to human platelet factor 4. Br J Haematol. 1978; 39(1): 129-146.

[26] Hundelshausen PV, Weber C. Platelets as Immune Cells: Bridging Inflammation and Cardiovascular Disease. Circ.Res. 2007; 100: 27-40.

[27] Bassenge E. Inhibition of platelet activation by endothelium derived relaxing factor EDRF/ NO and NO releasing dilator substances. Z Kardiol. 1991; 80(5): 17-21.

[28] Leeson CPM, Hingorani AD, Mullen MJ, Jeerooburkhan N, Kattenhorn M, Cole TJ, Muller DP, Lucas A, Humphries SE, Deanfield JE. Glu298Asp Endothelial Nitric Oxide Synthase Gene Polymorphism Interacts With Environmental and Dietary Factors to Influence Endothelial Function. Circ. Res. 2002; 90:1153-1158.

[29] Tempfer C, Rene M, Moreno, Anthony R. Genetic contributions of the endothelial nitric oxide synthase gene to ovulation and menopause in a mouse model. Fertil Steril. 2000; 73(5): 1025-1031.

Metadata

Repository Staff Only: item control page

Cogprints is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.