Catalase activity, allelic variations in the catalase gene and risk of kidney complications in patients with type 1 diabetes

Abstract

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. 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 G,n,tique de la N,phropathie Diab,tique (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. 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. 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.