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@article{562148, author = {Kaňková, Kateřina and Stejskalová, Andrea and Hertlová, Miluše and Znojil, Vladimír}, article_location = {United Kingdom}, article_number = {6}, keywords = {AGEs; complications; diabetic nephropathy; haplotype analysis; polymorphism; RAGE}, language = {eng}, issn = {0931-0509}, journal = {Nephrology Dialysis Transplantation}, title = {Haplotype analysis of the RAGE gene: identification of a haplotype marker for diabetic nephropathy in type 2 diabetes mellitus}, volume = {20}, year = {2005} }
TY - JOUR ID - 562148 AU - Kaňková, Kateřina - Stejskalová, Andrea - Hertlová, Miluše - Znojil, Vladimír PY - 2005 TI - Haplotype analysis of the RAGE gene: identification of a haplotype marker for diabetic nephropathy in type 2 diabetes mellitus JF - Nephrology Dialysis Transplantation VL - 20 IS - 6 SP - 1093-1102 EP - 1093-1102 PB - Oxford University Press SN - 09310509 KW - AGEs KW - complications KW - diabetic nephropathy KW - haplotype analysis KW - polymorphism KW - RAGE N2 - 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 SNPs in 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 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 P=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<0.003, two-tail Fisher-exact test); ORs 1.65 [95% CI 1.08 - 2.50], P=0.020 and 1.79 [95% CI 1.22 - 2.62], P=0.003, respectively. In survival analysis, duration of diabetes until the onset of DN (e.g. appearance of persistent proteinuria) was significantly different among RAGE2 diplotype groups (P<0.05); median DN-free interval was 9.6 years in RAGE2 +/+ homozygotes, 15.2 years in +/- heterozygotes and 17.0 years in the -/- combination. Conclusions: The RAGE2 haplotype is associated with DN in type 2 diabetics and with earlier DN onset, and thus can be regarded a marker for DN. ER -
KAŇKOVÁ, Kateřina, Andrea STEJSKALOVÁ, Miluše HERTLOVÁ a Vladimír ZNOJIL. Haplotype analysis of the RAGE gene: identification of a haplotype marker for diabetic nephropathy in type 2 diabetes mellitus. \textit{Nephrology Dialysis Transplantation}. United Kingdom: Oxford University Press, 2005, roč.~20, č.~6, s.~1093-1102. ISSN~0931-0509.
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