Functional impact of sequence variation in the promoter region of TGFB1.

Abstract:

:Pathological deregulation of the transforming growth factor, beta 1 (TGFB1) pathway has been implicated in the development of several major diseases, including cancers. Regulatory variation in the TGFB1 gene may lead to altered TGFB1 expression and activity, and thus, modulate an individual's susceptibility to disease. Here, we performed a study of the functional relevance of cis-acting regulatory variation in the proximal promoter region of the TGFB1 gene. In a previous study, 9 promoter polymorphisms were identified in the 2kb region upstream of the transcription start site and 9 distinct promoter haplotypes were inferred from a panel of individuals from 5 distinct continental population groups. Following experimental validation, we found that the 2 major haplotypes significantly influenced TGFB1 transcriptional activity in an allele-specific manner and that 3 of the SNPs (-1886G>A, -509C>T and -1550DEL/AGG) altered DNA-protein complex formation. Though the biological relevance of these findings remains to be verified, our study suggests that polymorphisms in the TGFB1 promoter could indeed influence gene expression and potentially contribute to the pathogenesis of TGFB1 related diseases.

journal_name

Int J Cancer

authors

Healy J,Dionne J,Bélanger H,Larivière M,Beaulieu P,Labuda D,Sinnett D

doi

10.1002/ijc.24526

subject

Has Abstract

pub_date

2009-09-15 00:00:00

pages

1483-9

issue

6

eissn

0020-7136

issn

1097-0215

journal_volume

125

pub_type

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