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A variant in the KCNQ1 gene predicts future type 2 diabetes and mediates impaired insulin secretion.

Jonsson, Anna LU ; Isomaa, Bo; Tuomi, Tiinamaija LU ; Taneera, Jalal LU ; Salehi, S Albert LU ; Nilsson, Peter LU ; Groop, Leif LU and Lyssenko, Valeriya LU (2009) In Diabetes 58(10). p.2409-2413
Abstract
Objective- Two independent genome wide association studies for type 2 diabetes in Japanese have recently identified common variants in the KCNQ1 gene to be strongly associated with type 2 diabetes. Here we studied whether a common variant in KCNQ1 would influence BMI, insulin secretion and action and predict future type 2 diabetes in subjects from Sweden and Finland. Research design and methods- Risk of type 2 diabetes conferred by KCNQ1 rs2237895 was studied in 2,830 type 2 diabetes cases and 3,550 controls from Sweden (Malmö Case-Control) and prospectively in 16,061 individuals from the Malmö Preventive Project (MPP). Association between genotype and insulin secretion/action was assessed cross-sectionally in 3,298 non-diabetic subjects... (More)
Objective- Two independent genome wide association studies for type 2 diabetes in Japanese have recently identified common variants in the KCNQ1 gene to be strongly associated with type 2 diabetes. Here we studied whether a common variant in KCNQ1 would influence BMI, insulin secretion and action and predict future type 2 diabetes in subjects from Sweden and Finland. Research design and methods- Risk of type 2 diabetes conferred by KCNQ1 rs2237895 was studied in 2,830 type 2 diabetes cases and 3,550 controls from Sweden (Malmö Case-Control) and prospectively in 16,061 individuals from the Malmö Preventive Project (MPP). Association between genotype and insulin secretion/action was assessed cross-sectionally in 3,298 non-diabetic subjects from the PPP-Botnia Study and longitudinally in 2,328 non-diabetic subjects from the Botnia Prospective Study (BPS). KCNQ1 expression (n=18) and glucose-stimulated insulin secretion (n=19) was measured in human islets from non-diabetic cadaver donors. Results. The C-allele of KCNQ1 rs2237895 was associated with increased risk of type 2 diabetes in both the case-control (OR 1.23 [1.12-1.34], p=5.6x10(-6)) and the prospective (OR 1.14 [1.06-1.22], p=4.8x10(-4)) studies. Furthermore, the C-allele was associated with decreased insulin secretion (CIR p=0.013; DI p=0.013) in the PPP-Botnia study and in the BPS at baseline (CIR p=3.6x10(-4); DI p=0.0058) and after follow-up (CIR p=0.0018; DI p=0.0030). C-allele carriers showed reduced glucose-stimulated insulin secretion in human islets (p=2.5x10(-6)). Conclusion. A common variant in the KCNQ1 gene is associated with increased risk of future type 2 diabetes in Scandinavians which partially can be explained by an effect on insulin secretion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
58
issue
10
pages
2409 - 2413
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000270776200029
  • pmid:19584308
  • scopus:70349640785
ISSN
1939-327X
DOI
10.2337/db09-0246
language
English
LU publication?
yes
id
337e926e-119f-4f79-95e8-95cd1cb9333f (old id 1453307)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19584308?dopt=Abstract
date added to LUP
2009-08-04 10:54:58
date last changed
2017-09-24 03:41:21
@article{337e926e-119f-4f79-95e8-95cd1cb9333f,
  abstract     = {Objective- Two independent genome wide association studies for type 2 diabetes in Japanese have recently identified common variants in the KCNQ1 gene to be strongly associated with type 2 diabetes. Here we studied whether a common variant in KCNQ1 would influence BMI, insulin secretion and action and predict future type 2 diabetes in subjects from Sweden and Finland. Research design and methods- Risk of type 2 diabetes conferred by KCNQ1 rs2237895 was studied in 2,830 type 2 diabetes cases and 3,550 controls from Sweden (Malmö Case-Control) and prospectively in 16,061 individuals from the Malmö Preventive Project (MPP). Association between genotype and insulin secretion/action was assessed cross-sectionally in 3,298 non-diabetic subjects from the PPP-Botnia Study and longitudinally in 2,328 non-diabetic subjects from the Botnia Prospective Study (BPS). KCNQ1 expression (n=18) and glucose-stimulated insulin secretion (n=19) was measured in human islets from non-diabetic cadaver donors. Results. The C-allele of KCNQ1 rs2237895 was associated with increased risk of type 2 diabetes in both the case-control (OR 1.23 [1.12-1.34], p=5.6x10(-6)) and the prospective (OR 1.14 [1.06-1.22], p=4.8x10(-4)) studies. Furthermore, the C-allele was associated with decreased insulin secretion (CIR p=0.013; DI p=0.013) in the PPP-Botnia study and in the BPS at baseline (CIR p=3.6x10(-4); DI p=0.0058) and after follow-up (CIR p=0.0018; DI p=0.0030). C-allele carriers showed reduced glucose-stimulated insulin secretion in human islets (p=2.5x10(-6)). Conclusion. A common variant in the KCNQ1 gene is associated with increased risk of future type 2 diabetes in Scandinavians which partially can be explained by an effect on insulin secretion.},
  author       = {Jonsson, Anna and Isomaa, Bo and Tuomi, Tiinamaija and Taneera, Jalal and Salehi, S Albert and Nilsson, Peter and Groop, Leif and Lyssenko, Valeriya},
  issn         = {1939-327X},
  language     = {eng},
  number       = {10},
  pages        = {2409--2413},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {A variant in the KCNQ1 gene predicts future type 2 diabetes and mediates impaired insulin secretion.},
  url          = {http://dx.doi.org/10.2337/db09-0246},
  volume       = {58},
  year         = {2009},
}