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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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Footnotes
☆Supported by Grants No. VS 96097 [ldquo ]Promotion of Research in Universities[rdquo ] and CEZ J07/98:141100002 from the Ministry of Education, Youth and Physical Education of the Czech Republic.
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Copyright
© 2001 Published by Elsevier Inc. All rights reserved.
