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

The formation of advanced glycation end products (AGEs) and oxidative stres s are supposed to play an important role in the development of diabetic lat e 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 th e impact of previously described polymorphisms in the RAGE gene (G82S, 1704 G/T, 2184A/G, and 2245G/A) on the glycoxidation status in non-insulin-depen dent diabetes mellitus (NIDDM). A total of 371 unrelated caucasian subjects were enrolled in the study. The NIDDM group consisted of 202 subjects, and the presence of late diabetic complications in 5 particular localizations was expressed as an index (I-compl). The nondiabetic group included 169 sub jects. Glycated hemoglobin (HbA(1c)), glycated stratum corneum proteins (Am adori, AGE), total carotenoids, alpha- and beta -carotene, gamma -tocophero l, lutein, lycopene, and alpha -tocopherol were measured in each subject. S tatistically significant differences in allele frequencies between the NIDD M and the nondiabetic groups were observed for the G82S and 2245G/A polymor phisms (P = .047 and .032, respectively. HbA(1c), Amadori, and AGE did not reveal any significant association with any of the polymorphisms analyzed. However, significant differences between subjects bearing "wild-type majori ty" genotypes 1704GG+2184AA and subjects with "mutated" genotypes were foun d for total carotenoids (P = .001), alpha -carotene (P = .046), beta -carot ene (P = .028), lutein (P = .001), lycopene (P = .006), and alpha -tocopher ol (P = .047). I-compl significantly correlated with the plasma levels of a ll antioxidants; (all P < .01), while no correlation of I-compl with glycat ion variables was observed. The newly identified intron polymorphisms in th e RAGE gene were proved to be associated with the antioxidant status in NID DM subjects. The extent of diabetic vascular disease is related to the plas ma levels of antioxidants. Copyright (C) 2001 by WB. Saunders Company.