HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Florez, J. C. Articles by Groop, L. Search for Related Content PubMed PubMed Citation Articles by Florez, J. C. Articles by Groop, L. Social Bookmarking                What's this?

The Krüppel-Like Factor 11 (KLF11) Q62R Polymorphism Is Not Associated With Type 2 Diabetes in 8,676 People

¹ Department of Molecular Biology and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
² Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
³ Department of Medicine, Harvard Medical School, Boston, Massachusetts
⁴ Medical and Population Genetics Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
⁵ Cancer Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
⁶ Department of Endocrinology, University Hospital MAS, Lund University, Malmö, Sweden
⁷ Department of Clinical Science, University Hospital MAS, Lund University, Malmö, Sweden
⁸ Department of Medicine, Helsinki University Central Hospital and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland
⁹ Folkhälsan Genetic Institute, Folkhälsan Research Center, Helsinki, Finland
¹⁰ University of Montreal Community Genomic Center, Chicoutimi Hospital, Chicoutimi, Quebec, Canada
¹¹ Genomics Collaborative Division, SeraCare LifeSciences, Cambridge, Massachusetts
¹² Department of Genetics, Harvard Medical School, Boston, Massachusetts
¹³ Divisions of Genetics and Endocrinology, Children’s Hospital, Boston, Massachusetts

Address correspondence and reprint requests to Jose C. Florez, Simches Research Building, CPZN 6820, Diabetes Unit/Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114. E-mail: jcflorez{at}partners.org

Abbreviations: AUC, area under the curve; GCI, Genomics Collaborative; OGTT, oral glucose tolerance test; SNP, single nucleotide polymorphism

Krüppel-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% CI 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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?