The p22 phox A640G gene polymorphism but not the C242T gene variation is associated with coronary heart disease in younger individuals

Gardemann, Andreas; Mages, Petra; Katz, Norbert; Tillmanns, Harald; Haberbosch, Werner

doi:10.1016/s0021-9150(99)00083-0

Cited by 102 publications

(106 citation statements)

References 24 publications

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“…Although our subgroups are small and as a consequence the power to detect differences is relatively low, the similar distribution of the CC-genotype in the patient and control populations provide evidence that the CC genotype was not associated with pre-eclampsia in a Dutch study population. Our findings in a Caucasian population are in line with the findings of Guzik et al, 4 Gardemann et al, 7 Li et al, 8 and Cahilly, 9 who found similar prevalences of the CC-genotype (45.4%, 44.3%, 45.6%, and 43.5%, respectively) and T-allele frequency (33%, 32%, 34%, and 34%, respectively) in large Caucasian populations. However, in Japanese control subjects the prevalence of the CC genotype was 73.6% 5 or 86.7% 6 compared with 51.3% in our Caucasian population.…”

Section: Discussionsupporting

confidence: 92%

The C242T-polymorphism of the NADPH/NADH oxidase gene p22phox subunit is not associated with pre-eclampsia

et al. 2002

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Pre-eclampsia is a pregnancy-related multisystem disorder characterised by elevation of blood pressure and proteinuria, in which oxidative stress may play an important role. Blood pressure is partly controlled by O − 2 production by NADPH/NADH oxidase and recently it was shown that a C242T substitution in the p22phox gene was associated with coronary artery disease, in which elevated blood pressure and oxidative stress are also important pathophysiologic features. Therefore we studied the prevalence of the C242T polymorphism in the NADPH/NADH oxidase gene in women with preeclampsia and/or haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome as compared with women with a normotensive pregnancy. DNA from control women (n = 78), women with pre-eclampsia (n = 40), HELLP syndrome (n = 9) or women with HELLP compli-

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Section: Discussionsupporting

confidence: 92%

The C242T-polymorphism of the NADPH/NADH oxidase gene p22phox subunit is not associated with pre-eclampsia

et al. 2002

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“…19 SNPs at positions À930, 640 and 242 of the gene modulate superoxide production and are linked to presence of hypertension as well as increased coronary artery disease risk among hypertensives. 3,4,20 The À930A/G SNP is located at the promoter region of the gene, and regulates transcriptional activation. Hypertensive GG homozygotes show enhanced transcription of the CYBA gene, increased production of the p22 phox subunit, upregulation of NADPH oxidase activity and, ultimately, increased ROS production.…”

Section: Resultsmentioning

confidence: 99%

The effect of p22phox −930A/G, A640G and C242T polymorphisms of NADPH oxidase on peripheral and central pressures in healthy, normotensive individuals

et al. 2010

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The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces superoxide, thus regulating redox state in the vessel wall. Three single-nucleotide polymorphisms (SNPs; À930A/G, A640G and C242T) of the p22 phox subunit have been associated with hypertension; however, their role in peripheral and central pressures in normotensive individuals has not been addressed. A total of 210 healthy, normotensive individuals were studied. Genotypes for the À930A/G, A640G and C242T polymorphisms were determined by polymerase chain reaction. Peripheral pressures were measured by mercury sphygmomanometer and aortic pressures by a validated device using applanation tonometry. Both peripheral and central pressures differed across À930A/G genotypes. G allele carriers showed higher levels of peripheral systolic blood pressure (PSBP; AA: 113±12, GG/AG: 119±12 mm Hg; Po0.01) and peripheral diastolic blood pressure (AA: 70±9, GG/AG: 73±10 mm Hg; Po0.05). Regarding central pressures, AA homozygotes had lower central systolic blood pressure (CSBP; AA: 103±12, GG/AG: 108 ± 12 mm Hg; Po0.01) and central diastolic blood pressure (AA: 71 ± 9, GG/AG: 74 ± 10 mm Hg; Po0.05). In multiple linear regression analysis, presence of the G allele (AG or GG) independently predicted CSBP. Blood pressure levels did not differ across A640G and C242T genotypes. The À930A/G polymorphism of p22 phox is a determinant of peripheral and central pressures in normotensive individuals. The G allele is associated with higher blood pressure in the brachial artery, as well as in the aorta. These findings further elucidate the role of this polymorphism in the regulation of blood pressure. In contrast, the A640G and C242T SNPs do not influence peripheral and central pressures in normotensives.

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“…We analysed five polymorphisms, three variants which have recently been associated with anthracyclineinduced cardiotoxicity 23 and, in addition, the other two NAD(P)H oxidase variants frequently discussed in relation to several clinical phenotypes. 17,18,22 The most extensively studied NAD(P)H oxidase polymorphism is the 242C4T variant of CYBA causing His4Tyr substitution at position 72. We could not demonstrate a consistent impact of this variant on enzyme activity.…”

Section: Discussionmentioning

confidence: 99%

“…20 In marked contrast, another group observed significantly higher superoxide production in carriers of the 242T allele. 21 Gardemann et al 22 delineated an association of the 640A4G polymorphism in the 3 0 UTR of CYBA with cardiovascular arterial disease, in particular in hypertensives. This SNP might modify processing or stability of p22phox mRNA.…”

Section: Kàmentioning

confidence: 99%

Genetic polymorphisms of NAD(P)H oxidase: variation in subunit expression and enzyme activity

et al. 2007

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Genetic polymorphisms in superoxide-producing NAD(P)H oxidase have been linked to cardiovascular diseases including anthracycline-induced cardiotoxicity. We quantified NAD(P)H oxidase activity in granulocytes of 81 healthy Caucasian volunteers (in addition, 51 in an independent confirmatory study) by chemiluminescence using the luminol analogue L-012. Expression of CYBA, NCF4 and RAC2 coding for NAD(P)H oxidase subunits was measured in whole blood cells in 59 study participants by realtime PCR. Of the five variants investigated (À930A4G, 242C4T, 640A4G in CYBA and the recently reported À368G4A in NCF4 and 7508T4A in RAC2), only CYBA 640A4G was consistently associated with superoxide production (640GG carriers 28% less than AA individuals, P ¼ 0.05 in each cohort, P ¼ 0.005 in combined analysis). RAC2 7508T4A was related to higher expression of RAC2 (P ¼ 0.02) and NCF4 (P ¼ 0.04). In summary, CYBA 640A4G rather than 242C4T was associated with reduced activity. The quantitatively moderate effect and the high intra-individual variability should be considered for further study design.

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The p22 phox A640G gene polymorphism but not the C242T gene variation is associated with coronary heart disease in younger individuals

Cited by 102 publications

References 24 publications

The C242T-polymorphism of the NADPH/NADH oxidase gene p22phox subunit is not associated with pre-eclampsia

The C242T-polymorphism of the NADPH/NADH oxidase gene p22phox subunit is not associated with pre-eclampsia

The effect of p22phox −930A/G, A640G and C242T polymorphisms of NADPH oxidase on peripheral and central pressures in healthy, normotensive individuals

Genetic polymorphisms of NAD(P)H oxidase: variation in subunit expression and enzyme activity

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