AI Article Synopsis
- Researchers studied the PTPN1 gene's promoter to see if certain variants might be linked to type 2 diabetes (T2D) and related metabolic traits among 174 T2D patients and 412 controls.
- They found one common variant (-1023C>A) and several rare variants, but after considering other risk factors, the associations with T2D diminished.
- The -51delA variant showed functional effects in cell experiments, reducing gene expression, but the study concluded that neither variant was significantly associated with T2D; larger studies are needed for confirmation.
Article Abstract
Background: Protein tyrosine phosphatase 1B (PTPN1) dephosphorylates insulin receptors and attenuates insulin signaling. Polymorphisms in the coding sequence of PTPN1 have been variably associated with type 2 diabetes (T2D). We hypothesized that variations within the PTPN1 promoter might contribute to the development of T2D and related metabolic traits.
Methods: We screened 2.0 kb of PTPN1 promoter in 174 T2D patients and 412 controls using PCR and denaturing HPLC. Association analysis was performed between diabetes and related traits and single-nucleotide polymorphism genotypes. We functionally tested 2 variants (-1023C>A and -51delA) by measuring their influence on luciferase activity in HepG2 cells and performing the electrophoretic mobility shift assay (EMSA).
Results: One common (-1023C>A) and 6 rare (-51delA, -451A>G, -467T>C, -1045G>A, -1286-3bp-del, and -1291-9bp-del) variants were identified in the PTPN1 promoter. The -1023(C) allele had significant association with T2D that disappeared after we adjusted for established diabetes risk factors. The alleles of -1023C>A and -51delA variants did not show significant effects on the biochemical markers after adjustment for established diabetes risk factors in the nondiabetic and diabetic groups separately. The -51delA variant decreased luciferase gene expression in HepG2 cells by 2-fold. EMSA revealed a weaker binding of -51delA to specific protein family proteins compared with the A allele. The -1023C>A variant had no influence in either experiment.
Conclusions: The PTPN1 promoter variants -1023C>A and -51delA (which appears to be functional) were not associated with T2D or related traits in this study but must be investigated in a larger population to reveal any potential metabolic association.
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| http://dx.doi.org/10.1373/clinchem.2007.088146 | DOI Listing |
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