Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.
Diabetes
; 45(6): 825-31, 1996 Jun.
Article
em En
| MEDLINE
| ID: mdl-8635661
ABSTRACT
NIDDM is a common heterogeneous disorder, the genetic basis of which has yet to be determined. The sulfonylurea receptor (SUR) gene, now known to encode an integral component of the pancreatic beta-cell ATP-sensitive potassium channel, IKATP, was investigated as a logical candidate for this disorder. The two nucleotide-binding fold (NBF) regions of SUR are known to be critical for normal glucose regulation of insulin secretion. Thus, single-strand conformational polymorphism analysis was used to find sequence changes in the two NBF regions of the SUR gene in 35 NIDDM patients. Eight variants were found; and three were evaluated in two Northern European white populations (Utah and the U.K.) 1) a missense mutation in exon 7 (S1370A) was found with equal frequency in patients (n = 223) and control subjects (n = 322); 2) an ACC-->ACT silent variant in exon 22 (T761T) was more common in patients than in control subjects (allele frequencies 0.07 vs. 0.02, P = 0.0008, odds ratio (OR) 3.01, 95% CI 1.54-5.87); and 3) an intronic t-->c change located at position -3 of the exon 24 splice acceptor site was also more common in patients than in control subjects (0.62 vs. 0.46, P < 0.0001, OR 1.91, 95% Cl 1.50-2.44). The combined genotypes of exon 22 C/T or T/T and intron 24 -3c/-3c occurred in 8.9% of patients and 0.5% of control subjects (P < 0.0001, OR 21.5, 95% CI 2.91-159.6). These results suggest that defects at the SUR locus may be a major contributor to the inherited basis of NIDDM in Northern European Caucasians.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Droga
/
Variação Genética
/
Canais de Potássio
/
Mutação Puntual
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Polimorfismo Conformacional de Fita Simples
/
Transportadores de Cassetes de Ligação de ATP
/
Canais de Potássio Corretores do Fluxo de Internalização
/
População Branca
/
Diabetes Mellitus Tipo 2
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
America do norte
/
Europa
Idioma:
En
Revista:
Diabetes
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos