To Analyze the Modifier Effect of NOS3 Gene in Hypertensive Patients of ADPKD
DOI:
https://doi.org/10.48165/fbc7je62Keywords:
VNTR genotypes, NOS3 gene, ADPKD, HypertensionAbstract
Background: Nitric oxide is important for the functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS). Hypertension has a strong genetic component, and the NOS3 gene, which encodes eNOS, represents an interesting candidate for contribution to the phenotype. The most clinically relevant polymorphisms in the NOS3 gene are a variable number tandem repeat (VNTR) in intron 4, and rs2070744 (T-786C) in the promoter region. Subjects and Methods: This study aims to investigate the association between these three polymorphisms in the NOS3 gene and modifier effect on age, progression of disease and hypertension in patients of ADPKD. Results: The present study carryout in the ADPKD patients admitted in NRI Medical College & Hospital. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on the progress of chronic kidney disease (CKD). A stratified analysis was also performed to assess the evidence of the modification of hypertension-CKD relationship among VNTR genotypes. Conclusion: The results of this study indicated that the polymorphism in NOS3 may be a genetic susceptibility factor for hypertension in the Indian population.
References
1. Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, et al. Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet. 1999;353:103-7.
2. Bergmann C, Kupper F, Schmitt CP, Vester U, Neuhaus TJ, Senderek J, et al. Multi-exon deletions of the PKHD1 gene cause autosomal recessive polycystic kidney disease (ARPKD). J Med Genet. 2005;42:e63.
3. Sharp AM, Messiaen LM, Page G, Antignac C, Gubler MC, Onuchic LF, et al. Comprehensive genomic analysis of PKHD1 mutations in ARPKD cohorts. J Med Genet. 2005;42:336-49.
4. Gabow PA. Autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1993;22:511-2.
5. Chapin HC, Caplan MJ. The cell biology of polycystic kidney disease. J Cell Biol. 2010;191:701-10.
6. Terryn S, Ho A, Beauwens R, Devuyst O. Fluid transport and cystogenesis in autosomal dominant polycystic kidney disease. Biochim Biophys Acta. 2011;1812:1314-21.
7. Gabow PA, Duley I, Johnson AM. Clinical profiles of gross hematuria in autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1992;20:140-3.
8. World Health Organization. Global status report on non communicable diseases 2010. Geneva: World Health Organization; 2011.
9. Persu A, Stoenoiu MS, Messiaen T et al. Modifier effect ofENOS in autosomal dominant polycystic kidney disease. Hum Mol Genet 2002; 11: 229–241
10. Mendelsohn ME, Karas RH. The protective effects of estrogenon the cardiovascular system. N Engl J Med 1999; 340: 1801–1811. 11. Noiri E, Satoh H, Taguchi J et al. Association of eNOSGlu298Asp polymorphism with end-stage renal disease.Hypertension 2002; 40: 535–540
12. Fischmann TO, Hruza A, Niu XD et al. Structuralcharacterization of nitric oxide synthase isoforms revealsstriking active-site conservation. Nat Struct Biol 1999; 6: 233–242
13. Tesauro M, Thompson WC, Rogliani P, Qi L, Chaudhary PP,Moss J. Intracellular processing of endothelial nitric oxidesynthase isoforms associated with differences in severity ofcardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci USA 2000;97: 2832–2835
14. Fairchild TA, Fulton D, Fontana JT, Gratton JP, McCabe TJ,Sessa WC. Acidic hydrolysis as a mechanism for the cleavageof the Glu(298)!Asp variant of human endothelial nitric-oxide synthase. J Biol Chem 2001; 276: 26674–26679.
15. Luscher TF, Noll G. Is it all in the genes...? Nitric oxide synthase and coronary vasospasm. Circulation 1999; 99: 2855–2857.
16. Ruschitzka F, Corti R, Noll G, Luscher TF. A rationale fortreatment of endothelial dysfunction in hypertension.J Hypertens 1999; 17: S25–S35.
17. Chapman AB, et al., Adv Chronic Kidney Dis, 2010;17:153–63. 18. Ecder T, et al., J Am Soc Nephrol, 2001;12:194–200. 19. Schrier RW, et al., Kidney Int, 2003;64:1792–9
20. Miyamoto Y, Saito Y, Kajiyama N, Yoshimura M, Shimasaki Y, Nakayama M, et al. Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension 1998;32(1):3-8.
21. Benjafield AV, Morris BJ. Association analyses of endothelial nitric oxide synthase gene polymorphisms in essential hypertension. Am J Hypertens 2000;13(9):994-8.
22. Li R, Lyn D, Lapu-Bula R, Oduwole A, Igho-Pemu P, Lankford B, et al. Relation of endothelial nitric oxide synthase gene to plasma nitric oxide level, endothelial function, and blood pressure in African Americans. Am J Hypertens 2004;17(7):560-7.
23. Patkar S, Charita BH, Ramesh C, Padma T. High risk of essential hypertension in males with intron 4 VNTR polymorphism of eNOS gene. Indian J Hum Genet 2009;15(2):49-53.
24. Persu A, Vinck WJ, El Khattabi O, Janssen RG, Paulussen AD, Devuyst O, et al. Influence of the endothelial nitric oxide synthase gene on conventional and ambulatory blood pressure: sib-pair analysis and haplotype study. J Hypertens 2005;23(4):759-65.
25. Merta M, Reiterova J, Tesar V, Stekrova J, Viklicky O. Influence of the endothelial nitric oxide synthase polymorphism on the progression of autosomal dominant polycystic kidney disease and IgA
nephropathy. Ren Fail 2002;24(5):585-93.
26. Persu A, Stoenoiu MS, Messiaen T, Davila S, Robino C, El-Khattabi O, et al. Modifier effect of ENOS in autosomal dominant polycystic kidney disease. Hum Mol Genet 2002;11(3):229-41.
27. Azurmendi P, Fraga A, Muchnik C, Dos Ramos Farias M, Galan F, Guerra D, et al. [Progression of autosomic dominant polycystic kidney disease. Influence of endothelial NO synthase (ecNOS) and renin angiotensin system gene polymorphisms]. Medicina (B Aires) 2004;64(2):139-42.
28. Asakimori Y, Yorioka N, Taniguchi Y, Ito T, Ogata S, Kyuden Y, Kohno N.T(-786)–>C polymorphism of the endothelial nitric oxide synthase geneinfluences the progression of renal disease. Nephron. 2002;91(4):747–51.
29. Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Ogawa H, Kugiyama K,Mizuno Y, Harada E, Nakamura S, Ito T, et al. T(-786)– > C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associatedwith myocardial infarction, especially without coronary organic stenosis. AmJ Cardiol. 2000;86(6):628–34.
30. Yoshimura M, Yasue H, Nakayama M, Shimasaki Y, Ogawa H, Kugiyama K,Saito Y, Miyamoto Y, Ogawa Y, Kaneshige T, et al. Genetic risk factors forcoronary artery spasm: significance of endothelial nitric oxide synthasegene T-786–>C and missense Glu298Asp variants. J Investig Med. 2000;48(5):367–74.
31. Jeerooburkhan N, Jones LC, Bujac S, Cooper JA, Miller GJ, Vallance P,Humphries SE, Hingorani AD. Genetic and environmental determinants ofplasma nitrogen oxides and risk of ischemic heart disease. Hypertension.2001;38(5):1054–61.
