A variation in 3′ utr of hptp1b increases specific gene expression and associates with insulin resistance

Rosa Di Paola, Lucia Frittitta, Giuseppe Miscio, Maura Bozzali, Roberto Baratta, Matra Centra, Daniela Spampinato, Maria Grazia Santagati, Tonino Ercolino, Carmela Cisternino, Teresa Soccio, Sandra Mastroianno, Vittorio Tassi, Peter Almgren, Antonio Pizzuti, Riccardo Vigneri, Vincenzo Trischitta

Research output: Contribution to journalArticle

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 HOMAIR 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; P <.01). 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).

Original languageEnglish
Pages (from-to)806-812
Number of pages7
JournalAmerican Journal of Human Genetics
Volume70
Issue number3
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Genetics

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    Di Paola, R., Frittitta, L., Miscio, G., Bozzali, M., Baratta, R., Centra, M., Spampinato, D., Santagati, M. G., Ercolino, T., Cisternino, C., Soccio, T., Mastroianno, S., Tassi, V., Almgren, P., Pizzuti, A., Vigneri, R., & Trischitta, V. (2002). A variation in 3′ utr of hptp1b increases specific gene expression and associates with insulin resistance. American Journal of Human Genetics, 70(3), 806-812. https://doi.org/10.1086/339270