Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism

Olavi Ukkola, Tuomo Rankinen, Timo Lakka, Arthur S. Leon, James S. Skinner, Jack H. Wilmore, D. C. Rao, Y. A. Kesäniemi, Claude Bouchard

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Protein tyrosine phosphatase IB (PTPN1) affects the regulation of insulin signaling and energy metabolism. We studied whether polymorphisms in the PTPN1 gene impact body fat distribution in the HERITAGE Family Study cohort in 502 white and 276 black subjects. Insulin sensitivity index, glucose disappearance index, acute insulin response to glucose (AIRglucosc), and the disposition index (DI) were obtained from the frequently sampled intravenous glucose tolerance test. White subjects with the G82G at the PTPN1 IVS6+G82A polymorphism had higher body fat levels (p = 0.031) and sum of eight skinfolds (p = 0.003) and highest subcutaneous fat on the limbs (p = 0.002). G82A subjects had the lowest AIRglucose (p - 0.005) and disposition index (p = 0.040). Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIRglucose (p from 0.006 to 0.010). The variant PTPN1 Pro387Leu was associated with lower fasting insulin level (p = 0.035) and glucose disappearance index (p = 0.038). In summary, PTPN1 IVS6+G82G homozygotes showed higher levels of all measures of adiposity. G82 allele heterozygotes are potentially at higher risk for type 2 diabetes. Gene-gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. The PTPN1 Pro387Leu variant was associated with lower,glucose tolerance.

Original languageEnglish (US)
Pages (from-to)829-834
Number of pages6
JournalObesity research
Volume13
Issue number5
DOIs
StatePublished - 2005

Keywords

  • Adiposity
  • Genotype
  • Insulin sensitivity
  • Protein tyrosine phosphate 1B

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