Polymorphisms and functions of the aldose reductase gene 5' regulatory region in Chinese patients with type 2 diabetes mellitus / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 209-213, 2002.
Artigo
em Inglês
| WPRIM
| ID: wpr-308117
ABSTRACT
<p><b>OBJECTIVE</b>To screen the 5' regulatory region of the aldose reductase (AR) gene for genetic variabilities causing changes in protein expression and affecting the promoter function.</p><p><b>METHODS</b>The screenings were carried out by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). All SSCP variants were submitted for DNA sequencing and inserted into the plasmid chloromycetin acetyl transferase (CAT) enhancer vector. The constructs were used to transfect Hela cells, and CAT assays were performed to assess promoter activity. Gel mobility shift and footprinting assays were also performed to determine the interaction between the DNA and nuclear proteins.</p><p><b>RESULTS</b>Two polymorphisms, C (-106) T and C (-12) G, were identified in the regulatory region in 123 Chinese control subjects and 145 patients with type 2 diabetes mellitus. The frequencies of genotypes WT/WT, WT/C (-12) G and WT/C (-106) T were not significantly different between the subjects and patients. In the patients with and without retinopathy, frequencies of WT/C (-106) T were 31.5% and 17.5% (P < 0.05) respectively, and the frequencies of WT/C (-12) G were 10.5% and 2.5% (P > 0.05) respectively. The total frequency of WT/C (-12) G and WT/C (-106) T in patients with retinopathy was 41.8%, significantly higher than that (20.0%) in patients without retinopathy (P < 0.025). The relative transcription activities of the wild-type, the C (-12) G and the C (-106) T were 15.7%, 31.0% and 32.2%, respectively. The results of DNA-protein interaction assays showed that these variations did not change the binding site of DNA with trans-acting factors.</p><p><b>CONCLUSION</b>The polymorphisms C (-12) G and C (-106) T strongly associated with diabetic retinopathy in the Chinese population have been identified in the regulatory region of the aldose reductase gene.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Polimorfismo Genético
/
Transcrição Gênica
/
Sítios de Ligação
/
Proteínas Recombinantes de Fusão
/
DNA
/
Células HeLa
/
Cloranfenicol O-Acetiltransferase
/
Química
/
China
/
Sequências Reguladoras de Ácido Nucleico
Tipo de estudo:
Estudo prognóstico
Limite:
Adulto
/
Feminino
/
Humanos
/
Masculino
País/Região como assunto:
Ásia
Idioma:
Inglês
Revista:
Chinese Medical Journal
Ano de publicação:
2002
Tipo de documento:
Artigo
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