Haplotype analysis of the RAGE gene: identification of a haplotype marker for diabetic nephropathy in type 2 diabetes mellitus

Background. Diabetic nephropathy (DN) represents a devastating complication of diabetes. Family clustering, heterogeneity in the onset and progression and results of segregation studies indicate that susceptibility to DN is a complex trait. Methods. Common single nucleotide polymorphisms in the RAGE (receptor of advanced glycation end-products) gene (−429T/C, −374T/A, G82S, 1704G/T, 2184A/G and 2245G/A) were studied in the association study comprising 605 Caucasian subjects by means of haplotype analysis in order to identify an eventual haplotype marker for DN in type 2 diabetes. Haplotypes were constructed computationally; frequencies were compared among groups of subjects with type 2 diabetes (DM) and DN, diabetics without DN and non-diabetics. Survival analysis was carried out to ascertain whether certain RAGE haplotypes influence onset of DN in type 2 diabetics. Results. Significant differences in haplotype frequencies among DM + DN vs DM non-DN and non-DM groups were found (P = 0.0007 and 0.0013, respectively; permutation test). Frequency of the RAGE2 haplotype containing minor alleles in positions −429 and 2184 (CTGGGG) in the DN group was significantly higher than in the two control groups (21.7% vs 12.8% and 13.8%, both Pcorr