Protein Tyrosine Phosphatase 1B Variant Associated with Fat Distribution and Insulin Metabolism

• Published in: Obesity (Silver Spring, Md.) Md.), 2005-05, Vol.13 (5), p.829-834
• Main Authors: Ukkola, Olavi, Rankinen, Tuomo, Lakka, Timo, Leon, Arthur S, Skinner, James S, Wilmore, Jack H, Rao, D.C, Kesäniemi, Y.A, Bouchard, Claude
• Format: Article
• Language: English
• Subjects: adipocytes; Adipose Tissue; adiposity; African Continental Ancestry Group; Body Composition - genetics; body fat distribution; Diabetes Mellitus, Type 2 - genetics; European Continental Ancestry Group; G-proteins; gene-for-gene relationship; genes; Genotype; Glucose Intolerance - genetics; Glucose Tolerance Test; Heterozygote; Homozygote; hormone metabolism; Humans; Insulin - metabolism; insulin resistance; Insulin Resistance - genetics; insulin secretion; insulin sensitivity; leptin; lipogenesis; Phenotype; Polymorphism, Genetic - genetics; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases - genetics; protein tyrosine phosphate 1B; receptors; Receptors, Cell Surface - genetics; Receptors, Leptin; regulatory proteins; Skinfold Thickness
• ISSN: 1071-7323; 1930-7381; 1550-8528; 1930-739X
• DOI: 10.1038/oby.2005.95

Protein tyrosine phosphatase 1B (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 (AIR[subscript glucose]), 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 AIR[subscript glucose] (p = 0.005) and disposition index (p = 0.040). Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR[subscript glucose] (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.