Sequence Analysis in Vicinity of Type 2 Diabetes Related SNP rs7903146

The SNP rs7903146 in human TCF7L2 gene has associated with type 2 diabetes (T2D) in multiple cohorts. TCF7L2 expression in human islets was increased in T2D, particularly in carriers of the TT genotype of SNP rs7903146. Over expression of TCF7L2 in human islets reduced glucose-stimulated insulin secretion. The question of why the TCF7L2 genetic variants effect it's self s expression remained unanswered. We analyzed the sequence of about 20 kb range in vicinity of rs7903146 SNP in combination with multiple bioinformatics programs in this study. We predicted 3 real pre-microRNAs on forward strand and 3 on reverse strand of 20 kb vicinity sequence of rs7903146 respectively. Five potential promoters on forward strand and seven on reverse strand were also predicted. The TFSEARCH web server predicted the type 2 diabetes risk "T" allele of rs7903146 SNP has an E4BP4 binding site and two CDX1 binding sites which the common "C" allele has not. We hypothesized that E4BP4, CDX1 and some microRNAs in intron3 transcribed with host gene or independently in intron3 of TCF7L2 are involved in predisposing T2D by TCF7L2 gene variants.