Large-scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP 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 β-cell ATP-sensitive potassium (KATP) channel, control insulin secretion. Common polymorphisms in these genes (ABCC8 exon 16-3t/c, exon 18 T/C, KCNJ11 E23K)...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2003
|
| _version_ | 1797067551190024192 |
|---|---|
| author | Gloyn, A Weedon, M Owen, K Turner, M Knight, B Hitman, G Walker, M Levy, J Sampson, M Halford, S McCarthy, M Hattersley, A Frayling, T |
| author_facet | Gloyn, A Weedon, M Owen, K Turner, M Knight, B Hitman, G Walker, M Levy, J Sampson, M Halford, S McCarthy, M Hattersley, A Frayling, T |
| author_sort | Gloyn, A |
| collection | OXFORD |
| description | The genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the β-cell ATP-sensitive 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 studies have been performed. We evaluated the role of these three variants by studying 2,486 U.K. subjects: 854 with type 2 diabetes, 1,182 population control subjects, and 150 parent-offspring type 2 diabetic trios. The E23K allele was associated with diabetes in the case-control study (odds ratio [OR] 1.18 [95% CI 1.04-1.34], P = 0.01) but did not show familial association with diabetes. Neither the exon 16 nor the exon 18 ABCC8 variants were associated with diabetes (1.04 [0.91-1.18], P = 0.57; 0.93 [0.71-1.23], P = 0.63, respectively). Meta-analysis of all case-control data showed that the E23K allele was associated with type 2 diabetes (K allele OR 1.23 [1.12-1.36], P = 0.000015; KK genotype 1.65 [1.34-2.02], P = 0.000002); but the ABCC8 variants were not associated. Our results confirm that E23K increases risk of type 2 diabetes and show that large-scale association studies are important for the identification of diabetes susceptibility alleles. |
| first_indexed | 2024-03-06T21:57:56Z |
| format | Journal article |
| id | oxford-uuid:4d915f27-4216-4b18-a986-68b32eb2020e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:57:56Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:4d915f27-4216-4b18-a986-68b32eb2020e2022-03-26T15:56:13ZLarge-scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4d915f27-4216-4b18-a986-68b32eb2020eEnglishSymplectic Elements at Oxford2003Gloyn, AWeedon, MOwen, KTurner, MKnight, BHitman, GWalker, MLevy, JSampson, MHalford, SMcCarthy, MHattersley, AFrayling, TThe genes ABCC8 and KCNJ11, which encode the subunits sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) of the β-cell ATP-sensitive 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 studies have been performed. We evaluated the role of these three variants by studying 2,486 U.K. subjects: 854 with type 2 diabetes, 1,182 population control subjects, and 150 parent-offspring type 2 diabetic trios. The E23K allele was associated with diabetes in the case-control study (odds ratio [OR] 1.18 [95% CI 1.04-1.34], P = 0.01) but did not show familial association with diabetes. Neither the exon 16 nor the exon 18 ABCC8 variants were associated with diabetes (1.04 [0.91-1.18], P = 0.57; 0.93 [0.71-1.23], P = 0.63, respectively). Meta-analysis of all case-control data showed that the E23K allele was associated with type 2 diabetes (K allele OR 1.23 [1.12-1.36], P = 0.000015; KK genotype 1.65 [1.34-2.02], P = 0.000002); but the ABCC8 variants were not associated. Our results confirm that E23K increases risk of type 2 diabetes and show that large-scale association studies are important for the identification of diabetes susceptibility alleles. |
| spellingShingle | Gloyn, A Weedon, M Owen, K Turner, M Knight, B Hitman, G Walker, M Levy, J Sampson, M Halford, S McCarthy, M Hattersley, A Frayling, T Large-scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes |
| title | Large-scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes |
| title_full | Large-scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes |
| title_fullStr | Large-scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes |
| title_full_unstemmed | Large-scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes |
| title_short | Large-scale association studies of variants in genes encoding the pancreatic beta-cell K-ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes |
| title_sort | large scale association studies of variants in genes encoding the pancreatic beta cell k atp channel subunits kir6 2 kcnj11 and sur1 abcc8 confirm that the kcnj11 e23k variant is associated with type 2 diabetes |
| work_keys_str_mv | AT gloyna largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT weedonm largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT owenk largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT turnerm largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT knightb largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT hitmang largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT walkerm largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT levyj largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT sampsonm largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT halfords largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT mccarthym largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT hattersleya largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes AT fraylingt largescaleassociationstudiesofvariantsingenesencodingthepancreaticbetacellkatpchannelsubunitskir62kcnj11andsur1abcc8confirmthatthekcnj11e23kvariantisassociatedwithtype2diabetes |