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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1453307
- author
- 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
- organization
- publishing date
- 2009
- 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
- 2016-04-01 12:14:54
- date last changed
- 2024-01-08 13:30:04
@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}},
doi = {{10.2337/db09-0246}},
volume = {{58}},
year = {{2009}},
}