A Cluster of Three Single Nucleotide Polymorphisms in the 3'-Untranslated Region of Human Glycoprotein PC-1 Gene Stabilizes PC-1 mRNA and Is Associated with Increased PC-1 Protein Content and Insulin Resistance-Related Abnormalities

Lucia Frittitta, Tonino Ercolino, Maura Bozzali, Alessandra Argiolas, Salvo Graci, Maria G. Santagati, Daniela Spampinato, Rosa Di Paola, Carmela Cisternino, Vittorio Tassi, Riccardo Vigneri, Antonio Pizzuti, Vincenzo Trischitta

Research output: Contribution to journalArticlepeer-review

Abstract

Glycoprotein PC-1 inhibits insulin signaling and, when overexpressed, plays a role in human insulin resistance. Mechanisms of PC-1 overexpression are unknown. We have identified a haplotype in the 3′-untranslated region of the PC-1 gene that may modulate PC-1 expression and confer an increased risk for insulin resistance. Individuals from Sicily, Italy, carrying the "P" haplotype (i.e., a cluster of three single nucleotide polymorphisms: G2897A, G2906C, and C2948T) were at higher risk (P <0.01) for insulin resistance and had higher (P <0.05) levels of plasma glucose and insulin during an oral glucose tolerance test and higher levels of cholesterol, HDL cholesterol, and systolic blood pressure. They also had higher (P <0.05-0.01) PC-1 protein content in both skeletal muscle and cultured skin fibroblasts. In CHO cells transfected with either P or wild-type cDNA, specific PC-1 mRNA half-life was increased for those transfected with P (t/2 = 3.73 ± 1.0 vs. 1.57 ± 0.2 h; P <0.01). In a population of different ethnicity (Gargano, East Coast Italy), patients with type 2 diabetes (the most likely clinical outcome of insulin resistance) had a higher P haplotype frequency than healthy control subjects (7.8 vs. 1.5%, P <0.01), thus replicating the association between the P allele and the insulin resistance-related abnormalities observed among Sicilians. In conclusion, we have identified a possible molecular mechanism for PC-1 overexpression that confers an increased risk for insulin resistance-related abnormalities.

Original languageEnglish
Pages (from-to)1952-1955
Number of pages4
JournalDiabetes
Volume50
Issue number8
Publication statusPublished - Aug 2001

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Fingerprint

Dive into the research topics of 'A Cluster of Three Single Nucleotide Polymorphisms in the 3'-Untranslated Region of Human Glycoprotein PC-1 Gene Stabilizes PC-1 mRNA and Is Associated with Increased PC-1 Protein Content and Insulin Resistance-Related Abnormalities'. Together they form a unique fingerprint.

Cite this