Associations between the CYBA 242C/T and the MPO -463G/A polymorphisms, oxidative stress and cardiovascular disease in chronic kidney disease patients.
Genetic variations in the NADPH/MPO system in chronic kidney disease (CKD) patients might lead to altered activity of these enzymes, and thus to altered risk for oxidative stress (OS) and cardiovascular disease (CVD). We evaluated the impact of 242C/T CYBA and -463G/A MPO polymorphisms on OS and CVD mortality in stage 5 CKD patients starting dialysis. Two hundred and fifty-seven patients were genotyped using Pyrosequencing. Plasmalogen [dimethylacetal (DMA) 16/C16:0] was used as OS marker. CVD was assessed from patient history and clinical symptoms. Prevalence of CVD was higher (35%) in GG patients (MPO) compared to AG (26%) and AA (0%) patients (p < 0.01). Patients with CC genotype (CYBA) had lower levels of DMA 16/C16:0 (ratio 0.071 +/- 0.003) compared to TT patients (0.089 +/- 0.006; p < 0.05). These patients also had increased CVD mortality compared to CT and TT patients (chi(2) 2.19; p < 0.05). We conclude that genetic variations in the NADPH/MPO system are associated with OS, presence of CVD and CVD-related mortality in CKD patients.
Grahl
Debora A
DA
Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Axelsson
Jonas
J
Nordfors
Louise
L
Heimburger
Olof
O
Bárány
Peter
P
Gao
Yuan-Zhe
YZ
Qureshi
Abdul Rashid
AR
Kato
Sawako
S
Watanabe
Makoto
M
Suliman
Mohamed
M
Riella
Miguel C
MC
Lindholm
Bengt
B
Stenvinkel
Peter
P
Pecoits-Filho
Roberto
R
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000201:enzymology / Q000235:genetics / Q000401:mortality
D009195:Peroxidase; D019255:NADPH Oxidases; C086986:CYBA protein, human