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Polymorphism screening of four genes encoding advanced glycation end-product putative receptors. Association study
O Poirier1, V Nicaud, N Vionnet
1Institut National de la Santé et de la Recherche Médicale INSERM U525/SC7, Paris, France.
Abstract:
Advanced glycation end-products (AGEs) may play an important role in the pathogenesis and progression of cardiovascular and renal complications of diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have been described. In this study, we scanned the sequence of the genes encoding these AGE receptors in 48 patients with type 1 diabetes and investigated the identified polymorphisms (n = 19) in 199 type 1 diabetic patients with nephropathy and 193 type 1 diabetic patients without nephropathy. Overall, none of the polymorphisms was strongly associated with nephropathy. The minor allele of a polymorphism located in the promoter region of the RAGE gene (C-1152A) conferred a weak protective effect (P < 0.05) and was associated with a longer duration of nephropathy-free diabetes (P = 0.08).
Insights
Advanced glycation end-products (AGEs) contribute to diabetic complications. Genetic variations in AGE receptors (RAGEs) were studied, with one RAGE gene polymorphism showing a weak protective effect against diabetic nephropathy.
Area of Science:
- Endocrinology
- Genetics
- Nephrology
Background:
- Advanced glycation end-products (AGEs) are implicated in diabetic cardiovascular and renal complications.
- Four putative AGE receptors (AGE-R1, AGE-R2, AGE-R3, and RAGE) are known.
- Genetic factors may influence susceptibility to diabetic nephropathy.
Purpose of the Study:
- To investigate the association between polymorphisms in AGE receptor genes and diabetic nephropathy in type 1 diabetes.
- To identify genetic variants that may confer protection or susceptibility to kidney complications in diabetes.
Main Methods:
- Gene sequencing of AGE receptor genes in 48 patients with type 1 diabetes.
- Genotyping of 19 identified polymorphisms in 199 type 1 diabetic patients with nephropathy and 193 without.
- Statistical analysis to assess the association between polymorphisms and nephropathy.
Main Results:
- No strong association was found between most investigated polymorphisms and diabetic nephropathy.
- A polymorphism in the RAGE gene promoter (C-1152A) showed a weak protective effect (P < 0.05).
- This RAGE polymorphism was linked to a longer duration of nephropathy-free diabetes (P = 0.08).
Conclusions:
- Genetic variations in AGE receptors do not appear to be a major determinant of diabetic nephropathy in type 1 diabetes.
- The RAGE C-1152A polymorphism may offer a slight protective effect against kidney complications.
- Further research is needed to elucidate the role of RAGE genetics in diabetic nephropathy.