Key result
Genetic variation at the AGT gene, including 235T and -6G alleles and specific haplotypes, was associated with increased susceptibility to diabetic nephropathy in T2DM patients.
Why the study?
Are renin and angiotensinogen gene polymorphisms associated with diabetic nephropathy in type 2 diabetes patients?
Case-Control (n=917)
Are renin and angiotensinogen gene polymorphisms associated with diabetic nephropathy in type 2 diabetes patients?
Genetic variation at the AGT gene, but not the renin C-4063T polymorphism, influences the risk of diabetic nephropathy in Tunisian type 2 diabetes patients.
AGT variants may signal higher nephropathy risk in T2DM; leaves open clinical utility pending prospective validation.
BACKGROUND: The association between renin C-4063T and angiotensinogen (AGT) T174M, M235T, and A-6G polymorphisms with diabetic nephropathy (DN) was investigated in Tunisian type 2 diabetes (T2DM) patients. METHODS: Study subjects comprised 917 T2DM patients (405 normoalbuminuric, 329 microalbuminuric and 185 macroalbuminuric). Genotyping was done by PCR-RFLP. RESULTS: Renin C-4063T allele and genotype frequencies were comparable between DN cases and normoalbuminuric controls. Although AGT 235T and -6G allele, and 235T/T and -6G/G genotype frequencies were higher in DN compared to normoalbuminuric patients, they were comparable between microalbuminuric or macroalbuminuric patients. Three-locus AGT haplotype analysis (A-6G/T174M/M235T) identified DN-protective (ATM, AMM, GTM) and DN-susceptible (GTM, ATT, GMT and AMT) haplotypes, and demonstrated enrichment of GTT haplotype in macroalbuminuric compared to microalbuminuric or normoalbuminuric patients. Regression analysis confirmed negative (AMM) and positive (GTM, ATT, GMT, AMT) association of AGT haplotypes with microalbuminuria, and negative (AMM) and positive (GTM and ATT) association of AGT haplotypes with macroalbuminuria. None of the AGT haplotypes was associated with DN severity. CONCLUSIONS: Genetic variation at the AGT gene influences the risk of nephropathy in T2DM patients but not extent of DN severity, and thus represents a potential DN genetic susceptibility locus worthy of replication.
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Mtiraoui et al. (2011) conducted a case-control in Type 2 diabetes and diabetic nephropathy (n=917). Renin C-4063T and angiotensinogen (AGT) T174M, M235T, and A-6G polymorphisms vs. Normoalbuminuric controls was evaluated on Association with diabetic nephropathy susceptibility and severity. Genetic variation at the AGT gene, including 235T and -6G alleles and specific haplotypes, was associated with increased susceptibility to diabetic nephropathy in T2DM patients.
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