Endothelial nitric oxide synthase and nicotinamide adenosine dinucleotide phosphate oxidase p22phox gene (C242T) polymorphisms and systemic lupus erythematosus in a Chinese Population

Abstract

Genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) and nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase p22phox are linked with the expression and/or progression of vascular disease. We hypothesized that these polymorphisms may influence the development and/or progression of systemic lupus erythematosus (SLE), given their linkage with vascular disease. DNA from patients with SLE (n = 90) and their age- and sex-matched controls (n = 86) from The Second Xiangya Hospital of Central South University was assessed for eNOS and NADPH oxidase p22phox polymorphisms. These polymorphisms were examined by restriction fragment length polymorphism—polymerase chain reaction. The allele frequency of the NADPH oxidase p22phox gene C242T polymorphisms significantly varied between the SLE patients and the controls. We found no association of the eNOS polymorphism with the development of renal disease. These results indicated that the etiology of patients with SLE is associated with NADPH oxidase p22phox gene C242T polymorphisms. There was no significant increased risk of SLE associated with eNOS polymorphisms in the Chinese population. Lupus (2010) 19, 192—196.

Keywords

endothelial nitric oxide synthase gene polymorphism nicotinamide adenosine dinucleotide phosphate oxidase p22phox systemic lupus erythematosus

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References

Marsden PA , Heng HH , Scherer SW , et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 1993; 268: 17478-17488.

Nakayama M. , Yasue H. , Yoshimura M. , et al. T-786→C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 1999; 99: 2864-2870.

Zanchi A. , Moczulski DK , Hanna LS , Wantman M. , Warram JH , Krolewski AS Risk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism. Kidney Int 2000; 57: 405-413.

Paradossi U. , Ciofini E. , Clerico A. , Botto N. , Biagini A. , Colombo MG Endothelial function and carotid intimamedia thickness in young healthy subjects among endothelial nitric oxide synthase Glu298Asp and T-786C polymorphisms . Stroke 2004; 35: 1305-1309.

Casas JP , Bautista LE , Humphries SE , Hingorani AD Endothelial nitric oxide synthase genotype and ischemic heart disease. Circulation 2004; 109: 1359-1365.

Nagase S. , Suzuki H. , Wang Y. , et al. Association of eNOS gene polymorphisms with end stage renal diseases. Mol Cell Biochem 2003; 244: 113-118.

Pearson JD Normal endothelial cell function. Lupus 2000 ; 9: 183-188.

Mohazzab-H KM , Kaminski PM , Wolin MS NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium. Am J Physiol 1994; 266: H2568-H2572.

Ushio-Fukai M. , Zafari AM , Fukui T. , et al. P22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem 1996; 271: 23317-23321.

10.

Guzik TJ , West NE , Black E. , et al. Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22phox gene on vascular superoxide production in atherosclerosis. Circulation 2000; 102: 1744-1747.

11.

Tang FY , Liu FY , Xie XW Association of angiotensin-converting enzyme and endothelial nitric oxide synthase gene polymorphisms with vascular disease in ESRD patients in a Chinese population. Mol Cell Biochem 2008; 319: 33-39.

12.

Allanore Y. , Borderie D. , Lemarechal H. , et al. Lack of association of eNOS (G894T) and p22phox NAPDH oxidase subunit (C242T) polymorphisms with systemic sclerosis in a cohort of French Caucasian patients. Clinica Chimica Acta 2004; 350: 51-55.

13.

Douglas G. , Reilly C. , Dooley MA , et al. Angiotensin-converting enzyme (insertion/deletion) and endothelial nitric oxide synthase polymorphisms in patients with systemic lupus erythematosus . J Rheumatol 2004; 31: 1756-1762.

14.

Tesauro M. , Thompson WC , Rogliani P. , et al. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci USA 2000; 97: 2832-2835.

15.

Wang XI , Sim AS , Wang MX , et al. Genotype dependent and cigarette specific effects on endothelial nitric oxide synthase gene expression and enzyme activity. FEBS Lett 2000; 471: 45-50.

16.

Veldman BA , Spiering W. , Doevendans PA , et al. The Glu298Asp polymorphism of the NOS3 gene as a determinant of baseline production of nitric oxide. J Hypertens 2002; 20: 2023-2027.

17.

Kim JU , Chang HK , Lee SS , et al. Endothelial nitric oxide synthase gene polymorphisms in Bechet’s disease and rheumatic diseases with vasculitis. Ann Rheum Dis 2003; 62: 1083-1087.

18.

Douglas G. , Cooper G. , Dooley MA , Gilkeson G. Endothelial nitric oxide synthase polymorphisms in systemic lupus erythematosus [abstract]. Arthritis Rheum 2002; 46(Suppl): S286.

19.

Kajiyama N. , Saito Y. , Miyamoto Y. , et al. Lack of association between T-786→C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene and essential hypertension. Hypertens Res 2000; 23: 561-565.

20.

Mugge A. The role of reactive oxygen species in atherosclerosis. Z Kardiol 1998; 87: 851-864.

21.

Inoue N. , Kawashima S. , Kanazawa K. , et al. Polymorphism of the NADH/NADPH oxidase p22phox gene in patients with coronary artery disease. Circulation 1998; 97: 135-137.

22.

Saha N. , Sanghera DK , Kamboh MI The p22phox polymorphism C242T is not associated with CHD risk in Asian Indians and Chinese. Eur J Clin Invest 1999; 29: 999-1002.