Linked Life Data

9568693

Source:http://linkedlifedata.com/resource/pubmed/id/9568693

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-5-7
pubmed:databankReference
pubmed:abstractText
The high-affinity sulfonylurea receptor (SUR1) is, as a subunit of the ATP-sensitive potassium channel, an important regulator of insulin secretion in the pancreatic beta-cell. The aim of this study was to examine if genetic variability of the SUR1 gene was associated with NIDDM or altered pancreatic beta-cell function. Mutational analysis of all the 39 SUR1 exons, including intron-exon boundaries, in 63 NIDDM patients revealed two missense variants, five silent variants in the coding region, and four intron variants. The two missense variants (Asp673Asn and Ser1369Ala) and two sequence variants (ACC-->ACT, Thr759Thr and a c-->t intron variant in position -3 of the exon 16 splice acceptor site) were examined for association with NIDDM and for a possible influence on insulin and C-peptide secretion after intravenous glucose and tolbutamide loads in a random sample of unrelated, healthy, young Danish Caucasians. The Asp673Asn variant in exon 14 was only identified in one NIDDM patient, and the allelic frequency of the Ser1369Ala was similar among 247 control subjects (0.38 [95% CI 0.34-0.42]) and 406 NIDDM patients (0.40 [0.37-0.43]). The allelic frequency of the silent exon 18 Thr775Thr variant was 0.051 (0.035-0.067) in NIDDM patients (n=392) and 0.027 (0.013-0.041) in control subjects (n=246; chi2=4.99, P=0.03). The allelic frequency of the intron variant was similar among NIDDM patients (0.45 [0.42-0.48]) and control subjects (0.44 [0.40-0.48]). Of 386 NIDDM patients, 17 had the combined genotype exon 18 C/T and intron -3c/-3t (0.044 [0.024-0.064]), whereas 3 of 243 control subjects had the same combined genotype (0.012 [0-0.026]; chi2=4.87, P=0.03; odds ratio: 3.69 [1.07-12.71]). Of 380 unrelated, healthy, young Danish Caucasians, 10 (0.026 [0.010-0.042]) had the combined at-risk genotype. These subjects had, on average, a 50% reduction in serum C-peptide and a 40% reduction in serum insulin responses upon tolbutamide injection (P=0.002 and P=0.05, respectively) but normal serum C-peptide and insulin responses upon glucose injection. In conclusion, a silent polymorphism in exon 18 of the SUR1 gene is associated with NIDDM in a Danish Caucasian population. In combination with an intron variant, the association is higher, and young, healthy carriers of the intragenic combination have reduced serum C-peptide and insulin responses to a tolbutamide load.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
598-605
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:9568693-ATP-Binding Cassette Transporters, pubmed-meshheading:9568693-Adolescent, pubmed-meshheading:9568693-Adult, pubmed-meshheading:9568693-Amino Acid Substitution, pubmed-meshheading:9568693-Diabetes Mellitus, Type 2, pubmed-meshheading:9568693-Exons, pubmed-meshheading:9568693-Female, pubmed-meshheading:9568693-Genotype, pubmed-meshheading:9568693-Glucose Tolerance Test, pubmed-meshheading:9568693-Humans, pubmed-meshheading:9568693-Insulin, pubmed-meshheading:9568693-Introns, pubmed-meshheading:9568693-Male, pubmed-meshheading:9568693-Molecular Sequence Data, pubmed-meshheading:9568693-Point Mutation, pubmed-meshheading:9568693-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:9568693-Potassium Channels, pubmed-meshheading:9568693-Potassium Channels, Inwardly Rectifying, pubmed-meshheading:9568693-Receptors, Drug, pubmed-meshheading:9568693-Tolbutamide
pubmed:year
1998
pubmed:articleTitle
Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene.
pubmed:affiliation
Steno Diabetes Center and Hagedorn Research Institute, Glostrup University Hospital, Copenhagen, Denmark.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't