Large-Scale Association Studies of Variants in Genes Encoding the Pancreatic -Cell KATP Channel Subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) Confirm That the KCNJ11 E23K Variant Is Associated With Type 2 Diabetes

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Brief Genetics Report Large-Scale Association Studies of Variants in Genes Encoding the Pancreatic -Cell KATP Channel Subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) Confirm That the KCNJ11 E23K Variant Is Associated With Type 2 Diabetes

The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the -cell ATPsensitive potassium (KATP) channel, control insulin secretion. Common polymorphisms in these genes (ABCC8 exon 16–3t/c, exon 18 T/C, KCNJ11 E23K) have been variably associated with type 2 diabetes, but no large ( 2,000 subjects) case-control stu...

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Association of the KCNJ11 variant E23K with type 2 diabetes in Indo-Trinidadians.

OBJECTIVE To examine the effect of genetic variation in KCNJ11 on the risk of Type 2 diabetes mellitus in Trinidadians. METHODS The coding and bordering intron-exon regions of the KCNJ11 gene were sequenced in 168 diabetic and 61 non-diabetic subjects who historically were thought to be of South Asian Indian ancestry as well as 66 diabetic and 59 non-diabetic subjects of African ancestry. All...

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Meta-analysis of association of common variants in the KCNJ11-ABCC8 region with type 2 diabetes.

KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11) and ABCC8 (ATP-binding cassette, subfamily C (CFTR/MRP), member 8) have been studied for association with type 2 diabetes in various ethnic populations with contradictory results. We performed a comprehensive meta-analysis for KCNJ11 rs5219, rs5210, rs5215, and ABCC8 rs757110 to evaluate the effect of these regions on geneti...

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Coexpression of the Type 2 Diabetes Susceptibility Gene Variants KCNJ11 E23K and ABCC8 S1369A Alter the ATP and Sulfonylurea Sensitivities of the ATP-Sensitive K+ Channel

OBJECTIVE In the pancreatic beta-cell, ATP-sensitive K(+) (K(ATP)) channels couple metabolism with excitability and consist of Kir6.2 and SUR1 subunits encoded by KCNJ11 and ABCC8, respectively. Sulfonylureas, which inhibit the K(ATP) channel, are used to treat type 2 diabetes. Rare activating mutations cause neonatal diabetes, whereas the common variants, E23K in KCNJ11 and S1369A in ABCC8, ar...

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The ATP-Sensitive K+ Channel ABCC8 S1369A Type 2 Diabetes Risk Variant Increases MgATPase Activity

Pancreatic β-cell ATP-sensitive K(+) (K(ATP)) channels are composed of Kir6.2 and SUR1 subunits encoded by the KCNJ11 and ABCC8 genes, respectively. Although rare monogenic activating mutations in these genes cause overt neonatal diabetes, the common variants E23K (KCNJ11) and S1369A (ABCC8) form a tightly heritable haplotype that is associated with an increased susceptibility to type 2 diabete...

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ژورنال

عنوان ژورنال: Diabetes

سال: 2003

ISSN: 0012-1797,1939-327X

DOI: 10.2337/diabetes.52.2.568