Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes
Holmkvist, Johan LU ; Almgren, Peter LU ; Lyssenko, Valeriya ; Lindgren, Cecilia M ; Eriksson, Karl-Fredrik LU ; Isomaa, Bo ; Tuomi, Tiinamaija LU
; Nilsson, Peter
LU
and Groop, Leif
LU
(2008)
In Diabetes
57(6).
p.1738-1744
- Abstract
- OBJECTIVE-Mutations in the hepatocyte nuclear factor (HNF)-1 alpha, HNF-4 alpha, glucokinase (GCK), and HNF-1 beta genes cause maturity-onset diabetes of the young (MODY), but it is not known whether common variants in these genes predict future type 2 diabetes. RESEARCH DESIGN AND METHODS-We tested 14 previously associated polymorphisms in HNF-1 alpha, HNF-4 alpha, GCK, and HNF-1 beta for association with type 2 diabetes-related traits and future risk of type 2 diabetes in 2,293 individuals from the Botnia study (Finland) and in 15,538 individuals from the Malmo Preventive Project (Sweden) with a total follow-up >360,000 years. RESULTS-The polymorphism rs1169288 in HNF-1 alpha strongly predicted future type 2 diabetes (hazard ratio... (More)
- OBJECTIVE-Mutations in the hepatocyte nuclear factor (HNF)-1 alpha, HNF-4 alpha, glucokinase (GCK), and HNF-1 beta genes cause maturity-onset diabetes of the young (MODY), but it is not known whether common variants in these genes predict future type 2 diabetes. RESEARCH DESIGN AND METHODS-We tested 14 previously associated polymorphisms in HNF-1 alpha, HNF-4 alpha, GCK, and HNF-1 beta for association with type 2 diabetes-related traits and future risk of type 2 diabetes in 2,293 individuals from the Botnia study (Finland) and in 15,538 individuals from the Malmo Preventive Project (Sweden) with a total follow-up >360,000 years. RESULTS-The polymorphism rs1169288 in HNF-1 alpha strongly predicted future type 2 diabetes (hazard ratio [HR] 1.2, P = 0.0002). Also, SNPs rs4810424 and rs3212198 in HNF-4a nominally predicted future type 2 diabetes (HR 1.3 [95% CI 1.0-1.6], P = 0.03; and 1.1 [1.0-1.2], P = 0.04). The rs2144908 polymorphism in HNF-4 alpha was associated with elevated rate of hepatic glucose production during a hyperinsulinemic-euglycemic clamp (P = 0.03) but not with deterioration of insulin secretion over time. The SNP rs1799884 in the GCK promoter was associated with elevated fasting plasma glucose (fPG) concentrations that remained unchanged during the follow-up period (P = 0.4; SE 0.004 [-0.003-0.007]) but did not predict future type 2 diabetes (HR 0.9 [0.8 -1.0], P = 0.1). Polymorphisms in HNF-1 beta (transcription factor 2 [TCF2]) did not significantly influence insulin or glucose values nor did they predict future type 2 diabetes. CONCLUSIONS-In conclusion, genetic variation in both HNF-1 alpha and HNF-4 alpha predict future type 2 diabetes, whereas variation in the GCK promoter results in a sustained but subtle elevation of fPG that is not sufficient to increase risk for future type 2 diabetes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1201421
- author
- Holmkvist, Johan
LU
; Almgren, Peter
LU
; Lyssenko, Valeriya
; Lindgren, Cecilia M
; Eriksson, Karl-Fredrik
LU
; Isomaa, Bo
; Tuomi, Tiinamaija
LU
; Nilsson, Peter
LU
and Groop, Leif
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 57
- issue
- 6
- pages
- 1738 - 1744
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- wos:000256611600038
- scopus:48249139502
- pmid:18332101
- pmid:18332101
- ISSN
- 1939-327X
- DOI
- 10.2337/db06-1464
- language
- English
- LU publication?
- yes
- id
- b98ec17e-a9f7-4781-8a50-2b2cde25fa04 (old id 1201421)
- date added to LUP
- 2016-04-01 14:28:46
- date last changed
- 2024-03-27 17:35:04
@article{b98ec17e-a9f7-4781-8a50-2b2cde25fa04,
abstract = {{OBJECTIVE-Mutations in the hepatocyte nuclear factor (HNF)-1 alpha, HNF-4 alpha, glucokinase (GCK), and HNF-1 beta genes cause maturity-onset diabetes of the young (MODY), but it is not known whether common variants in these genes predict future type 2 diabetes. RESEARCH DESIGN AND METHODS-We tested 14 previously associated polymorphisms in HNF-1 alpha, HNF-4 alpha, GCK, and HNF-1 beta for association with type 2 diabetes-related traits and future risk of type 2 diabetes in 2,293 individuals from the Botnia study (Finland) and in 15,538 individuals from the Malmo Preventive Project (Sweden) with a total follow-up >360,000 years. RESULTS-The polymorphism rs1169288 in HNF-1 alpha strongly predicted future type 2 diabetes (hazard ratio [HR] 1.2, P = 0.0002). Also, SNPs rs4810424 and rs3212198 in HNF-4a nominally predicted future type 2 diabetes (HR 1.3 [95% CI 1.0-1.6], P = 0.03; and 1.1 [1.0-1.2], P = 0.04). The rs2144908 polymorphism in HNF-4 alpha was associated with elevated rate of hepatic glucose production during a hyperinsulinemic-euglycemic clamp (P = 0.03) but not with deterioration of insulin secretion over time. The SNP rs1799884 in the GCK promoter was associated with elevated fasting plasma glucose (fPG) concentrations that remained unchanged during the follow-up period (P = 0.4; SE 0.004 [-0.003-0.007]) but did not predict future type 2 diabetes (HR 0.9 [0.8 -1.0], P = 0.1). Polymorphisms in HNF-1 beta (transcription factor 2 [TCF2]) did not significantly influence insulin or glucose values nor did they predict future type 2 diabetes. CONCLUSIONS-In conclusion, genetic variation in both HNF-1 alpha and HNF-4 alpha predict future type 2 diabetes, whereas variation in the GCK promoter results in a sustained but subtle elevation of fPG that is not sufficient to increase risk for future type 2 diabetes.}},
author = {{Holmkvist, Johan and Almgren, Peter and Lyssenko, Valeriya and Lindgren, Cecilia M and Eriksson, Karl-Fredrik and Isomaa, Bo and Tuomi, Tiinamaija and Nilsson, Peter and Groop, Leif}},
issn = {{1939-327X}},
language = {{eng}},
number = {{6}},
pages = {{1738--1744}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes}},
url = {{http://dx.doi.org/10.2337/db06-1464}},
doi = {{10.2337/db06-1464}},
volume = {{57}},
year = {{2008}},
}