Polymorphisms in the human glutathione transferase Kappa (GSTK1) promoter alter gene expression.
The level of glutathione transferase Kappa (GSTK1-1) has been correlated with obesity (Liu et.al. 2008 PNAS 105: 18302-7) and a polymorphism in the hGSTK1 promoter has been associated with insulin secretion and fat deposition (Gao et al 2009 Endocr J 56: 487-94). We searched for additional polymorphisms that may influence GSTK1-1 function or expression. Two SNPs were identified in the 5' non-coding region. A SNP at -1308 that occurs in Chinese subjects is predicted to eliminate a FXR/RXR transcription factor-binding site and causes a 55% increase in transcription rate in HepG2 cells and a 59% decrease in HEK293 cells. These data suggest that the impact of this polymorphism is complex and tissue specific. A SNP at -1032 alters a methylation site and represses transcription by 38%. These observations provide the first functional insight into genetic factors that regulate hGSTK1 expression and may directly influence insulin secretion and fat deposition.
Shield
Alison J
AJ
Division of Molecular Biosciences, John Curtin School of Medical Research, Australian National University, Acton, ACT 2601, Australia.
Murray
Tracy P
TP
Cappello
Jean Y
JY
Coggan
Marjorie
M
Board
Philip G
PG
D005260:Female; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D007328:Insulin; C487896:GSTK1 protein, human; D005982:Glutathione Transferase