Signals derived from the metabolism of glucose in pancreatic β-cells lead to insulin secretion via the closure of ATP-sensitive K+ channels (KATP). The cloning of the gene encoding the (β-cell inward rectifier Kir6.2 (Bir), a subunit of the β-cell KATP channel, provided the opportunity to look for mutations in this gene that might contribute to the impaired insulin secretion of NIDDM. By single-strand conformational polymorphism (SSCP) analysis on 35 Northern-European Caucasian patients with NIDDM, six sequence variants were detected: Glu10gag→Lys10aag (E10K), Glu23gag→Lys23aag (E23K), Leu270ctg→Val270gtg (L270V), Ile337atc→Val337gtc (I337V), and two silent mutations. Allelic frequencies for the missense variants were compared between the NIDDM group (n = 306) and nondiabetic control subjects (n = 175) and did not differ between the two groups. Pairwise allelic associations indicated significant linkage disequilibrium between the variants in Kir6.2 and between them and a nearby pancreatic β-cell sulfonylurea receptor (SUR1) missense variant (S1370A), but these linkage disequilibria did not differ between the NIDDM and control groups. The results of these studies thus revealed that mutations in the coding region of Kir6.2 1) were not responsible for the previously noted association of the SUR1 variants with NIDDM (Inoue H et al., Diabetes 45:825–831, 1996) and 2) did not contribute to the impaired insulin secretion characteristic of NIDDM in Caucasian patients.
Sequence Variants in the Pancreatic Islet β-Cell Inwardly Rectifying K+ Channel Kir6.2 (Bir) Gene: Identification and Lack of Role in Caucasian Patients with NIDDM
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Hiroshi Inoue, Jorge Ferrer, Margaret Warren-Perry, Yun Zhang, Helen Millns, Robert C Turner, Steven C Elbein, Carol L Hampe, Brian K Suarez, Nobuya Inagaki, Susumu Seino, M Alan Permutt; Sequence Variants in the Pancreatic Islet β-Cell Inwardly Rectifying K+ Channel Kir6.2 (Bir) Gene: Identification and Lack of Role in Caucasian Patients with NIDDM. Diabetes 1 March 1997; 46 (3): 502–507. https://doi.org/10.2337/diab.46.3.502
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