Polymorphisms in the human glutathione transferase Kappa (GSTK1) promoter alter gene expression

Alison J. Shield; Tracy P. Murray; Jean Y. Cappello; Marjorie Coggan; Philip G. Board

doi:10.1016/j.ygeno.2010.02.007

Polymorphisms in the human glutathione transferase Kappa (GSTK1) promoter alter gene expression

Alison J. Shield, Tracy P. Murray, Jean Y. Cappello, Marjorie Coggan, Philip G. Board^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	299-305
Number of pages	7
Journal	Genomics
Volume	95
Issue number	5
DOIs	https://doi.org/10.1016/j.ygeno.2010.02.007
Publication status	Published - May 2010

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title = "Polymorphisms in the human glutathione transferase Kappa (GSTK1) promoter alter gene expression",

abstract = "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.",

keywords = "Glutathione transferase Kappa, Promoter, Single nucleotide polymorphisms",

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T1 - Polymorphisms in the human glutathione transferase Kappa (GSTK1) promoter alter gene expression

AU - Shield, Alison J.

AU - Murray, Tracy P.

AU - Cappello, Jean Y.

AU - Coggan, Marjorie

AU - Board, Philip G.

PY - 2010/5

Y1 - 2010/5

N2 - 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.

AB - 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.

KW - Glutathione transferase Kappa

KW - Promoter

KW - Single nucleotide polymorphisms

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DO - 10.1016/j.ygeno.2010.02.007

M3 - Article

SN - 0888-7543

VL - 95

SP - 299

EP - 305

JO - Genomics

JF - Genomics

IS - 5

ER -

Polymorphisms in the human glutathione transferase Kappa (GSTK1) promoter alter gene expression

Abstract

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