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 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...

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Published in:	Metabolism, clinical and experimental Vol. 50; no. 10; pp. 1152 - 1160
Main Authors:	Ka[ncaron]kov[aacute], Kate[rcaron]ina, M[aacute]rov[aacute], Ivana, Z[aacute]hejsk[yacute], Ji[rcaron][iacute], Mu[zcaron][iacute]k, Jan, Stejskalov[aacute], Andrea, Znojil, Vladim[iacute]r, V[aacute]cha, Ji[rcaron][iacute]
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-10-2001 Elsevier
Subjects:	Alleles Biological and medical sciences Carotenoids - blood Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Female Genotype Glycated Hemoglobin A - analysis Glycation End Products, Advanced - metabolism Humans Introns Male Medical sciences Middle Aged Oxidative Stress Polymorphism, Genetic Receptor for Advanced Glycation End Products Receptors, Immunologic - genetics Receptors, Immunologic - metabolism Skin - metabolism Endocrinopathy Human Pathophysiology Pathogenesis Finished product Exploration Antioxidant Non insulin dependent diabetes Genetic determinism Glycation Gene Polymorphism Biological receptor
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Summary:	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 (I compl). The nondiabetic group included 169 subjects. Glycated hemoglobin (HbA 1c), 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. HbA 1c, 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). I compl significantly correlated with the plasma levels of all antioxidants (all P [lt ] .01), while no correlation of I compl 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0026-0495 1532-8600
DOI:	10.1053/meta.2001.26757