A Variation in 3' UTR of HPTP1B Increases Specific Gene Expression and Associates with Insulin Resistance

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2002 Feb 8

PMID 11833006

Citations 42

Authors

Rosa Di Paola

Lucia Frittitta

Giuseppe Miscio

Maura Bozzali

Roberto Baratta

Marta Centra

Daniela Spampinato

Maria Grazia Santagati

Tonino Ercolino

Carmela Cisternino

Teresa Soccio

Sandra Mastroianno

Vittorio Tassi

Peter Almgren

Antonio Pizzuti

Riccardo Vigneri

Vincenzo Trischitta

Affiliations

Soon will be listed here.

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 plus minus 1,879 copies/40 ng RNA vs. 2,983 plus minus 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).

Citing Articles

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Sun Y, Dinenno F, Tang P, Kontaridis M Front Cardiovasc Med. 2024; 11:1445739.

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