Catalase activity, allelic variations in the catalase gene and risk of kidney complications in patients with type 1 diabetes.
OBJECTIVE
Oxidative stress is involved in the pathogenesis of diabetic nephropathy. The antioxidant enzyme catalase plays a key role in redox regulation in the kidney. We investigated associations of catalase gene (CAT) polymorphisms and plasma catalase activity with diabetic nephropathy in type 1 diabetic patients.


METHODS
We genotyped nine single nucleotide polymorphisms (SNPs) in the CAT region in participants from the Survival Genetic Nephropathy (SURGENE) (340 French participants, 10 year follow-up) and the Génétique de la Néphropathie Diabétique (GENEDIAB) (444 Belgian and French participants, 8 year follow-up) study cohorts. Replication was performed in a Brazilian cross-sectional cohort (n = 451). Baseline plasma catalase activity was measured in SURGENE (n = 120) and GENEDIAB (n = 391) participants.


RESULTS
The A allele of rs7947841 was associated with the prevalence of incipient (OR 2.79, 95% CI 1.21, 6.24, p = 0.01) and established or advanced nephropathy (OR 5.72, 95% CI 1.62, 22.03, p = 0.007), and with the incidence of renal events, which were defined as new cases of microalbuminuria or progression to a more severe stage of nephropathy during follow-up (HR 1.82, 95% CI 1.13, 2.81, p = 0.01) in SURGENE participants. The same risk allele was associated with incipient nephropathy (OR 3.13, 95% CI 1.42, 7.24, p = 0.004) and with the incidence of end-stage renal disease (ESRD) (HR 2.11, 95% CI 1.23, 3.60, p = 0.008) in GENEDIAB participants. In both cohorts, the risk allele was associated with lower catalase activity. Associations with incipient and established or advanced nephropathy were confirmed in the replication cohort.


CONCLUSIONS
CAT variants were associated with the prevalence and incidence of diabetic nephropathy and ESRD in type 1 diabetic patients. Our results confirm the protective role of catalase against oxidative stress in the kidney.
Inserm Research Unit 695, 16 rue Henri Huchard, 75018, Paris, France.
Kamel
K
Mohammedi
Thiago A
TA
Patente
Naïma
N
Bellili-Muñoz
Fathi
F
Driss
Maria Beatriz
MB
Monteiro
Ronan
R
Roussel
Elizabeth J
EJ
Pavin
Nathalie
N
Seta
Frédéric
F
Fumeron
Mirela J
MJ
Azevedo
Luis H
LH
Canani
Samy
S
Hadjadj
Michel
M
Marre
Maria Lúcia
ML
Corrêa-Giannella
Gilberto
G
Velho
D000328:Adult; D001530:Belgium; D001938:Brazil; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D003430:Cross-Sectional Studies; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005787:Gene Frequency; D014644:Genetic Variation; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors
D002374:Catalase