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

• Published in: Diabetes (New York, N.Y.) Vol. 45; no. 6; pp. 825 - 831
• Main Authors: Inoue, H., Ferrer, J., Welling, C. M., Elbein, S. C., Hoffman, M., Mayorga, R., Warren-Perry, M., Zhang, Y., Millns, H., Turner, R., Province, M., Bryan, J., Permutt, M. A., Aguilar-Bryan, L.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01.06.1996
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.45.6.825

Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians. H Inoue , J Ferrer , C M Welling , S C Elbein , M Hoffman , R Mayorga , M Warren-Perry , Y Zhang , H Millns , R Turner , M Province , J Bryan , M A Permutt and L Aguilar-Bryan Division of Metabolism, Diabetes and Endocrinology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. 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.