Genotype and tissue-specific effects on alternative splicing of the transcription factor 7-like 2 gene in humans.

ABSTRACT:

Context

Noncoding single-nucleotide polymorphisms (SNPs) within the TCF7L2 gene are confirmed risk factors for type 2 diabetes, but the mechanism by which they increase risk is unknown.

Objective

We hypothesized that associated SNPs alter TCF7L2 splicing and that splice forms have altered biological roles.

Design

Splice forms and 5' and 3' untranslated regions were characterized in sc adipose, muscle, liver, HepG2 cells, pancreas, and islet. Isoform-specific transcript levels were quantified in sc adipose. Alternative splice forms were characterized in HepG2 liver cells under glucose and insulin conditions and in SGBS cells with differentiation. Major isoforms were characterized by transfection.

Setting

The study was conducted at an ambulatory general clinical

SUBMITTER: Mondal AK 

PROVIDER: S-EPMC2841530 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature