We have analysed SNPs within nine KLF genes and we were not able to show a genetic T2D association in our population. A similar study in a Japanese population also showed no evidence for an association with other variants of the same KLF genes analysed in our study (KLF2, -3, -5, -12, -13 and KLF16 ). However, it is worth noting that some KLF genes are not covered extensively with HapMap genotyped SNPs. In fact, this was the case for KLF15 and KLF16 gene regions, where at the start of this study no Taqman® assays were available. Therefore, we decided to screen these genes for common SNPs. Since we analysed in our study all frequent SNPs without any positive results, we conclude that the KLF15 and KLF16 genes are not likely to be associated with T2D in a French population.
A limitation of our study is the two-staged design, through which we may have missed a weak but true association with T2D. However, the use of T2D patients with affected first degree relatives and controls sharing the same environment as the cases in set 1, probably increased our power to detect an association with T2D. A second limitation of this study is the fact that it does not cover all the genetic variability of the KLF genes. However, our subsequent genome wide association analysis with 1,363 individuals also did not show significant T2D associations for variants of these genes, making it unlikely the nine KLFs play a major role in genetic T2D susceptibility.
We hypothesised that KLF genes could be associated with genetic susceptibility for T2D, based on their role in adipogenesis. In particularly, KLF2 is implicated in the regulation of PPARγ , which is a target gene implicated in the genetic susceptibility for T2D. Therefore, we studied this gene more extensively and genotyped 9 SNPs. Also for KLF2 variants, we did not observe an association with T2D in this French population. In addition, a previous study of KLF2 variants and body weight control in another French population did not observe an association with adipose tissue-related traits . From these results, it seems unlikely that the genetic variability of the KLF2 gene plays a mayor role in susceptibility to T2D or obesity.