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The Kruppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people

Florez, Jose C. ; Saxena, Richa ; Winckler, Wendy ; Burtt, Noel P. ; Almgren, Peter LU ; Bengtsson Boström, Kristina LU ; Tuomi, Tiinamaija ; Gaudet, Daniel ; Ardlie, Kristin G. and Daly, Mark J. , et al. (2006) In Diabetes 55(12). p.3620-3624
Abstract
Kruppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite > 99% power to detect an association... (More)
Kruppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite > 99% power to detect an association of the previously published magnitude, Q62R was not associated with type 2 diabetes (pooled odds ratio 0.97 [95% Cl 0.88-1.08], P = 0.63). In a subset of normoglycemic individuals, we did not observe significant differences in various insulin traits according to genotype at KLF11 Q62R. We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
55
issue
12
pages
3620 - 3624
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000242446800051
  • scopus:33845516306
  • pmid:17130512
ISSN
1939-327X
DOI
10.2337/db06-0867
language
English
LU publication?
yes
id
f7fa0043-5cbc-40ed-b8d2-dae722f1814c (old id 685284)
date added to LUP
2016-04-01 16:17:03
date last changed
2021-09-01 02:47:31
@article{f7fa0043-5cbc-40ed-b8d2-dae722f1814c,
  abstract     = {Kruppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite > 99% power to detect an association of the previously published magnitude, Q62R was not associated with type 2 diabetes (pooled odds ratio 0.97 [95% Cl 0.88-1.08], P = 0.63). In a subset of normoglycemic individuals, we did not observe significant differences in various insulin traits according to genotype at KLF11 Q62R. We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk.},
  author       = {Florez, Jose C. and Saxena, Richa and Winckler, Wendy and Burtt, Noel P. and Almgren, Peter and Bengtsson Boström, Kristina and Tuomi, Tiinamaija and Gaudet, Daniel and Ardlie, Kristin G. and Daly, Mark J. and Altshuler, David and Hirschhorn, Joel N. and Groop, Leif},
  issn         = {1939-327X},
  language     = {eng},
  number       = {12},
  pages        = {3620--3624},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {The Kruppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people},
  url          = {http://dx.doi.org/10.2337/db06-0867},
  doi          = {10.2337/db06-0867},
  volume       = {55},
  year         = {2006},
}