A Variation in 3′ UTR of hPTP1B Increases Specific Gene Expression and Associates with Insulin Resistance

• Published in: American journal of human genetics Vol. 70; no. 3; pp. 806 - 812
• Main Authors: Di Paola, Rosa, Frittitta, Lucia, Miscio, Giuseppe, Bozzali, Maura, Baratta, Roberto, Centra, Marta, Spampinato, Daniela, Santagati, Maria Grazia, Ercolino, Tonino, Cisternino, Carmela, Soccio, Teresa, Mastroianno, Sandra, Tassi, Vittorio, Almgren, Peter, Pizzuti, Antonio, Vigneri, Riccardo, Trischitta, Vincenzo
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.03.2002; University of Chicago Press; The American Society of Human Genetics
• Subjects: 3' Untranslated Regions - genetics; Adult; Basic Medicine; Biological and medical sciences; Blood Glucose - analysis; Blood Pressure - genetics; Cell Line; Cholesterol - blood; Dactinomycin - pharmacology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exons - genetics; Fasting - blood; Female; Gene Expression Regulation - drug effects; Gene Frequency; Genotype; Humans; Insulin - blood; Insulin Resistance - genetics; Introns - genetics; Male; Medical and Health Sciences; Medical Genetics; Medical Genetics and Genomics (including Gene Therapy); Medical sciences; Medicin och hälsovetenskap; Medicinsk genetik; Medicinsk genetik och genomik (Här ingår: Genterapi); Medicinska och farmaceutiska grundvetenskaper; Mutation - genetics; Polymorphism, Single Nucleotide - genetics; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - genetics; RNA Stability - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Triglycerides - blood; Endocrinopathy; Human; Enzyme; Pathogenesis; Genetic variant; Phosphoric monoester hydrolases; Genotype; Esterases; Gene expression; Genetic determinism; Insulin; Target tissue resistance; Phenotype; Gene; Risk factor; Hydrolases; Protein-tyrosine-phosphatase
• ISSN: 0002-9297; 1537-6605; 1537-6605
• DOI: 10.1086/339270

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; 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).