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A variation in 3 ' UTR of hPTP1B increases specific gene expression and associates with insulin resistance

Di Paola, R; Frittitta, L; Miscio, G; Bozzali, M; Baratta, R; Centra, M; Spampinato, D; Santagati, MG; Ercolino, T and Cisternino, C, et al. (2002) In American Journal of Human Genetics 70(3). p.806-812
Abstract
Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR) index (P = .006), serum triglycerides (P = .0002), and total/HDL cholesterol ratio (P = .025) and, among female individuals, higher blood pressure (P = .01). Similar data were also obtained in a family-based association study by use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the 1484insG variant showed also PTP1B... (More)
Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR) index (P = .006), serum triglycerides (P = .0002), and total/HDL cholesterol ratio (P = .025) and, among female individuals, higher blood pressure (P = .01). Similar data were also obtained in a family-based association study by use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the 1484insG variant showed also PTP1B mRNA overexpression in skeletal muscle (6,166 +/- 1,879 copies/40 ng RNA vs. 2,983 +/- 1,620;). Finally, PTP1B mRNA stability was significantly higher (P < .01) in human embryo kidney 293 cells transfected with 1484insG PTP1B, as compared with those transfected with wild-type PTP1B. Our data indicate that the 1484insG allele causes PTP1B overexpression and plays a role in insulin resistance. Therefore, individuals carrying the 1484insG variant might particularly benefit from PTP1B inhibitors, a promising new tool for treatment of insulin resistance (Kennedy and Ramachandran 2000). (Less)
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American Journal of Human Genetics
volume
70
issue
3
pages
806 - 812
publisher
Cell Press
external identifiers
  • pmid:11833006
  • wos:000173880000026
  • scopus:0036008643
ISSN
0002-9297
DOI
10.1086/339270
language
English
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yes
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b5610a8d-3bed-4276-ab4a-a13265391531 (old id 343595)
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2007-08-02 16:28:23
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2017-10-22 03:53:44
@article{b5610a8d-3bed-4276-ab4a-a13265391531,
  abstract     = {Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR) index (P = .006), serum triglycerides (P = .0002), and total/HDL cholesterol ratio (P = .025) and, among female individuals, higher blood pressure (P = .01). Similar data were also obtained in a family-based association study by use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the 1484insG variant showed also PTP1B mRNA overexpression in skeletal muscle (6,166 +/- 1,879 copies/40 ng RNA vs. 2,983 +/- 1,620;). Finally, PTP1B mRNA stability was significantly higher (P &lt; .01) in human embryo kidney 293 cells transfected with 1484insG PTP1B, as compared with those transfected with wild-type PTP1B. Our data indicate that the 1484insG allele causes PTP1B overexpression and plays a role in insulin resistance. Therefore, individuals carrying the 1484insG variant might particularly benefit from PTP1B inhibitors, a promising new tool for treatment of insulin resistance (Kennedy and Ramachandran 2000).},
  author       = {Di Paola, R and Frittitta, L and Miscio, G and Bozzali, M and Baratta, R and Centra, M and Spampinato, D and Santagati, MG and Ercolino, T and Cisternino, C and Soccio, T and Mastroianno, S and Tassi, V and Almgren, Peter and Pizzuti, A and Vigneri, R and Trischitta, V},
  issn         = {0002-9297},
  language     = {eng},
  number       = {3},
  pages        = {806--812},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {A variation in 3 ' UTR of hPTP1B increases specific gene expression and associates with insulin resistance},
  url          = {http://dx.doi.org/10.1086/339270},
  volume       = {70},
  year         = {2002},
}