Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.

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Citation

Inoue H, Ferrer J, Welling CM, Elbein SC, Hoffman M, Mayorga R, Warren-Perry M, Zhang Y, Millns H, Turner R, Province M, Bryan J, Permutt MA, Aguilar-Bryan L

Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.

Diabetes. 1996 Jun;45(6):825-31.

PubMed ID
8635661 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
ATP-binding cassette sub-family C member 8Q09428Details