Single nucleotide polymorphisms in the gene encoding Krüppel-like factor 7 are associated with type 2 diabetes.
OBJECTIVE
Although genetic susceptibility plays an important role in the pathogenesis of type 2 diabetes, most of the genes that influence susceptibility to type 2 diabetes have yet to be identified. Krüppel-like transcription factors are known to play important roles in development and cell differentiation, and have recently been implicated in the pathogenesis of type 2 diabetes. The present study aimed to examine the associations of single nucleotide polymorphisms (SNPs) in genes encoding members of the Krüppel-like-factor (KLF) family with type 2 diabetes in a large cohort of Japanese subjects.


METHODS
We genotyped 33 SNP loci found in 12 KLF genes in subjects with type 2 diabetes and in subjects from the general population using the PCR-Invader assay. We also examined the effects of the overexpression of KLF7 on adipogenesis in 3T3-L1 cells.


RESULTS
We identified a significant association between an SNP in KLF7 and type 2 diabetes (A vs C: p=0.004 after Bonferroni's correction, odds ratio=1.59, 95% CI 1.27-2.00). The expression of Klf7 decreased in response to the differentiation of 3T3-L1 adipocytes, and the overexpression of KLF7 resulted in significant inhibition of adipogenesis in 3T3-L1 cells.


CONCLUSIONS
These results indicate that the gene encoding KLF7 is a novel candidate for conferring genetic susceptibility to type 2 diabetes.
Kanazawa
A
A
Laboratory for Diabetic Nephropathy, SNP Research Centre, Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
Kawamura
Y
Y
Sekine
A
A
Iida
A
A
Tsunoda
T
T
Kashiwagi
A
A
Tanaka
Y
Y
Babazono
T
T
Matsuda
M
M
Kawai
K
K
Iiizumi
T
T
Fujioka
T
T
Imanishi
M
M
Kaku
K
K
Iwamoto
Y
Y
Kawamori
R
R
Kikkawa
R
R
Nakamura
Y
Y
Maeda
S
S
D016475:3T3 Cells; D000818:Animals; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D005810:Multigene Family; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C480503:KLF7 protein, human; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors