Publication details

Polymorphisms 1704G/T and 2184A/G in the RAGE gene are associated with antioxidant status



Year of publication 2001
Type Article in Periodical
Magazine / Source Metabolism: Clinical and Experimental
MU Faculty or unit

Faculty of Medicine

Field Genetics and molecular biology
Description BACKGROUND: The formation of advanced glycation end products (AGEs) and oxidative stress are supposed to play an important role in the development of diabetic late complications. AGEs can bind to several binding sites including Receptor of Advanced Glycation End products (RAGE). AGE-RAGE interaction results in free radical generation. The aim of the present study was to investigate the impact of previously described polymorphisms in the RAGE gene (G82S, 1704G/T, 2184A/G and 2245G/A) on the glycoxidation status in NIDDM. METHODS: A total of 371 unrelated Caucasian subjects were enrolled in the study. The NIDDM group comprised 202 subjects, the presence of late diabetic complications in five particular localizations was expressed as an index (Icompl). The non-diabetic group comprised 169 subjects. Glycated hemoglobin (HbA1c), glycated stratum corneum proteins (Amadori, AGE), total carotenoids, a- and b-carotene, g-tocopherol, lutein, lycopene and a-tocopherol were measured in each subject. RESULTS: Statistically significant differences in allele frequencies between the NIDDM and the non-diabetic groups were observed for the G82S and 2245G/A polymorphisms (P=0.047 and 0.032, resp.). HbA1c, Amadori and AGE did not reveal any significant association with any of the polymorphisms analyzed. However, significant differences between subjects bearing "wild type majority" genotypes 1704GG+2184AA and subjects with "mutated" genotypes were found for total carotenoids (P=0.001), a-carotene (P=0.046), b-carotene (P=0.028), lutein (P=0.001), lycopene (P=0.006) and a-tocopherol (P=0.047). Icompl significantly correlated with the plasma levels of all antioxidants (all P<0.01), while no correlation of Icompl with glycation variables was observed. CONCLUSIONS: The newly identified intron polymorphisms in the RAGE gene were proved to be associated with the antioxidant status in NIDDM subjects. The extent of diabetic vascular disease is related to the plasma levels of antioxidants.
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