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

  • Kate[rcaron]ina Ka[ncaron]kov[aacute]
    Affiliations
    From the Department of Pathophysiology, Faculty of Medicine, Masaryk University; Department of Food Chemistry and Biotechnology, Faculty of Chemistry, Technical University; and Department of Dermatology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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  • Ivana M[aacute]rov[aacute]
    Affiliations
    From the Department of Pathophysiology, Faculty of Medicine, Masaryk University; Department of Food Chemistry and Biotechnology, Faculty of Chemistry, Technical University; and Department of Dermatology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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  • Ji[rcaron][iacute] Z[aacute]hejsk[yacute]
    Affiliations
    From the Department of Pathophysiology, Faculty of Medicine, Masaryk University; Department of Food Chemistry and Biotechnology, Faculty of Chemistry, Technical University; and Department of Dermatology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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  • Jan Mu[zcaron][iacute]k
    Affiliations
    From the Department of Pathophysiology, Faculty of Medicine, Masaryk University; Department of Food Chemistry and Biotechnology, Faculty of Chemistry, Technical University; and Department of Dermatology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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  • Andrea Stejskalov[aacute]
    Affiliations
    From the Department of Pathophysiology, Faculty of Medicine, Masaryk University; Department of Food Chemistry and Biotechnology, Faculty of Chemistry, Technical University; and Department of Dermatology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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  • Vladim[iacute]r Znojil
    Affiliations
    From the Department of Pathophysiology, Faculty of Medicine, Masaryk University; Department of Food Chemistry and Biotechnology, Faculty of Chemistry, Technical University; and Department of Dermatology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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  • Ji[rcaron][iacute] V[aacute]cha
    Affiliations
    From the Department of Pathophysiology, Faculty of Medicine, Masaryk University; Department of Food Chemistry and Biotechnology, Faculty of Chemistry, Technical University; and Department of Dermatology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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      Abstract

      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 non[ndash ]insulin-dependent 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 (Icompl). The nondiabetic group included 169 subjects. Glycated hemoglobin (HbA1c), glycated stratum corneum proteins (Amadori, AGE), total carotenoids, [alpha ]- and [beta ] -carotene, [gamma ]-tocopherol, lutein, lycopene, and [alpha ]-tocopherol were measured in each subject. Statistically significant differences in allele frequencies between the NIDDM and the nondiabetic groups were observed for the G82S and 2245G/A polymorphisms (P = .047 and .032, respectively. HbA1c, Amadori, and AGE did not reveal any significant association with any of the polymorphisms analyzed. However, significant differences between subjects bearing [ldquo ]wild-type majority[rdquo ] genotypes 1704GG+2184AA and subjects with [ldquo ]mutated[rdquo ] genotypes were found for total carotenoids (P = .001), [alpha ]-carotene (P = .046), [beta ]-carotene (P = .028), lutein (P = .001), lycopene (P = .006), and [alpha ]-tocopherol (P = .047). Icompl significantly correlated with the plasma levels of all antioxidants (all P [lt ] .01), while no correlation of Icompl with glycation variables was observed. 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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