Analysis of KLF transcription factor family gene variants in type 2 diabetes.
BACKGROUND
The Krüppel-like factor (KLF) family consists of transcription factors that can activate or repress different genes implicated in processes such as differentiation, development, and cell cycle progression. Moreover, several of these proteins have been implicated in glucose homeostasis, making them candidate genes for involvement in type 2 diabetes (T2D).


METHODS
Variants of nine KLF genes were genotyped in T2D cases and controls and analysed in a two-stage study. The first case-control set included 365 T2D patients with a strong family history of T2D and 363 normoglycemic individuals and the second set, 750 T2D patients and 741 normoglycemic individuals, all of French origin. The SNPs of six KLF genes were genotyped by Taqman SNP Genotyping Assays. The other three KLF genes (KLF2, -15 and -16) were screened and the identified frequent variants of these genes were analysed in the case-control studies.


RESULTS
Three of the 28 SNPs showed a trend to be associated with T2D in our first case-control set (P < 0.10). These SNPs, located in the KLF2, KLF4 and KLF5 gene were then analysed in our second replication set, but analysis of this set and the combined analysis of the three variants in all 2,219 individuals did not show an association with T2D in this French population. As the KLF2, -15 and -16 variants were representative for the genetic variability in these genes, we conclude they do not contribute to genetic susceptibility for T2D.


CONCLUSIONS
It is unlikely that variants in different members of the KLF gene family play a major role in T2D in the French population.
Gutiérrez-Aguilar
Ruth
R
UMR8090, CNRS, Institute of Biologie/Institute Pasteur de Lille, Lille, France. Ruth@good.ibl.fr
Benmezroua
Yamina
Y
Vaillant
Emmanuel
E
Balkau
Beverley
B
Marre
Michel
M
Charpentier
Guillaume
G
Sladek
Rob
R
Froguel
Philippe
P
Neve
Bernadette
B
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors
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