The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load.
<h4>Background</h4>Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1) have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs228322...
Guardado en:
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Public Library of Science (PLoS)
2009
|
Materias: | |
Acceso en línea: | https://doaj.org/article/0d58a0cd81f841f78d30959a06c09843 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:0d58a0cd81f841f78d30959a06c09843 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:0d58a0cd81f841f78d30959a06c098432021-11-25T06:22:11ZThe type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load.1932-620310.1371/journal.pone.0005872https://doaj.org/article/0d58a0cd81f841f78d30959a06c098432009-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19516902/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1) have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897) on estimates of glucose stimulated insulin release.<h4>Methodology/principal findings</h4>Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean+/-SD: (CC) 277+/-160 vs. (AC) 280+/-164 vs. (AA) 299+/-200 pmol/l, p = 0.008) after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007), incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02) among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228.<h4>Conclusion</h4>The minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function.Johan HolmkvistKarina BanasikGitte AndersenHiroyuki UnokiThomas Skot JensenCharlotta PisingerKnut Borch-JohnsenAnnelli SandbaekTorsten LauritzenSören BrunakShiro MaedaTorben HansenOluf PedersenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 6, p e5872 (2009) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Johan Holmkvist Karina Banasik Gitte Andersen Hiroyuki Unoki Thomas Skot Jensen Charlotta Pisinger Knut Borch-Johnsen Annelli Sandbaek Torsten Lauritzen Sören Brunak Shiro Maeda Torben Hansen Oluf Pedersen The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. |
description |
<h4>Background</h4>Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1) have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897) on estimates of glucose stimulated insulin release.<h4>Methodology/principal findings</h4>Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean+/-SD: (CC) 277+/-160 vs. (AC) 280+/-164 vs. (AA) 299+/-200 pmol/l, p = 0.008) after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007), incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02) among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228.<h4>Conclusion</h4>The minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function. |
format |
article |
author |
Johan Holmkvist Karina Banasik Gitte Andersen Hiroyuki Unoki Thomas Skot Jensen Charlotta Pisinger Knut Borch-Johnsen Annelli Sandbaek Torsten Lauritzen Sören Brunak Shiro Maeda Torben Hansen Oluf Pedersen |
author_facet |
Johan Holmkvist Karina Banasik Gitte Andersen Hiroyuki Unoki Thomas Skot Jensen Charlotta Pisinger Knut Borch-Johnsen Annelli Sandbaek Torsten Lauritzen Sören Brunak Shiro Maeda Torben Hansen Oluf Pedersen |
author_sort |
Johan Holmkvist |
title |
The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. |
title_short |
The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. |
title_full |
The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. |
title_fullStr |
The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. |
title_full_unstemmed |
The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. |
title_sort |
type 2 diabetes associated minor allele of rs2237895 kcnq1 associates with reduced insulin release following an oral glucose load. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2009 |
url |
https://doaj.org/article/0d58a0cd81f841f78d30959a06c09843 |
work_keys_str_mv |
AT johanholmkvist thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT karinabanasik thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT gitteandersen thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT hiroyukiunoki thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT thomasskotjensen thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT charlottapisinger thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT knutborchjohnsen thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT annellisandbaek thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT torstenlauritzen thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT sorenbrunak thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT shiromaeda thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT torbenhansen thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT olufpedersen thetype2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT johanholmkvist type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT karinabanasik type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT gitteandersen type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT hiroyukiunoki type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT thomasskotjensen type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT charlottapisinger type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT knutborchjohnsen type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT annellisandbaek type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT torstenlauritzen type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT sorenbrunak type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT shiromaeda type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT torbenhansen type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload AT olufpedersen type2diabetesassociatedminoralleleofrs2237895kcnq1associateswithreducedinsulinreleasefollowinganoralglucoseload |
_version_ |
1718413785537970176 |