Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study.
The enzyme xanthine oxidoreductase (XOR) generates uric acid in the terminal steps of the purine metabolism; meanwhile reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension.



Among 2769 participants (48.3% men; mean age 40.7 years) randomly recruited from European populations, we genotyped 25 tagging XOR SNPs and measured blood pressure (BP) at baseline and follow-up (median 8.8 years). The relation between variants of the XOR gene with changes in pulse pressure and mean arterial pressure over time; and incidence of hypertension, were analyzed.



Compared with nonminor allele carriers, pulse pressure increased approximately 2 mmHg more in minor allele carriers of rs11904439 (P = 0.01), whereas mean arterial pressure and DBP increased approximately 1 mmHg less in minor allele carriers of rs2043013 (P = 0.01). In 2050, participants normotensive at baseline, hazard ratios contrasting risk of hypertension in minor allele carriers vs. nonminor allele carriers were 1.31 (95% confidence interval 1.03-1.68; P = 0.02) and 1.69 (95% confidence interval 1.11-2.57; P = 0.01) for rs11904439 and rs148756340, respectively. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in SBP from baseline to follow-up and the serum levels of uric acid at baseline (n = 1949) were not associated with XOR.



Pending confirmation, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in BP and in the risk of hypertension.
aDivision of Rheumatology, Department of Internal Medicine, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre+, Maastricht, The Netherlands bStudies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium cFirst Department of Cardiology and Hypertension, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland dInstitute of Internal and Preventive Medicine, Novosibirsk, Russian Federation eDepartment of Clinical and Experimental Medicine, University of Padova, Padova fDepartment of Health Sciences, University of Milan, Milan, Italy gFaculty of Medicine, Charles University, Pilsen, Czech Republic hSchool of Nephrology, Vita-Salute San Raffaele University iInstitute of Biomedical Technologies, Italian National Centre of Research, Milan, Italy jVitaK R & D Group kDepartment of Epidemiology, CAPHRI School for Public Health and Primary Care, CARIM School for Cardiovascular Sciences, and MaCSBio Maastricht Centre for Systems Biology, Maastricht University, Maastricht, The Netherlands.
Lieke E J M
LE
Scheepers
Fang-Fei
FF
Wei
Katarzyna
K
Stolarz-Skrzypek
Sofia
S
Malyutina
Valérie
V
Tikhonoff
Lutgarde
L
Thijs
Erika
E
Salvi
Cristina
C
Barlassina
Jan
J
Filipovský
Edoardo
E
Casiglia
Yuri
Y
Nikitin
Kalina
K
Kawecka-Jaszcz
Paolo
P
Manunta
Daniele
D
Cusi
Annelies
A
Boonen
Jan A
JA
Staessen
Ilja C W
IC
Arts
D000328:Adult; D062186:Arterial Pressure / Q000235:genetics; D001530:Belgium / Q000453:epidemiology; D001794:Blood Pressure / Q000235:genetics*; D018153:Czech Republic / Q000453:epidemiology; D003971:Diastole / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012426:Russia / Q000453:epidemiology; D014527:Uric Acid / Q000097:blood*; D044465:White People / Q000235:genetics; D014969:Xanthine Oxidase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
D014527:Uric Acid; D014969:Xanthine Oxidase