Human Molecular Genetics Advance Access originally published online on June 30, 2004
Human Molecular Genetics 2004 13(17):1885-1892; doi:10.1093/hmg/ddh196
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Human Molecular Genetics, Vol. 13, No. 17 © Oxford University Press 2004; all rights reserved
Single nucleotide polymorphisms in protein tyrosine phosphatase 1ß (PTPN1) are associated with essential hypertension and obesity
1Stanford Human Genome Center and 2Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA, 3Division of Biostatistics and Bioinformatics, National Health Research Institutes, Taipei, Taiwan, 4Department of Internal Medicine, National Taiwan University, Taipei, Taiwan, 5Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, 6Division of Cardiology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, 7Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles, CA, USA and 8Pacific Health Research Institute, Honolulu, HI, USA
Received April 14, 2004; Accepted June 15, 2004
Protein tyrosine phosphatase 1ß (PTP-1ß) is involved in the regulation of several important physiological pathways. It regulates both insulin and leptin signaling, and interacts with the epidermal- and platelet-derived growth factor receptors. The gene is located on human chromosome 20q13, and several rare single nucleotide polymorphisms (SNPs) have been shown to be associated with insulin resistance and diabetes in different populations. As part of our ongoing investigations into the genetic basis of hypertension, we examined common sequence variants in the gene for association with hypertension, obesity and altered lipid profile in two populations of Japanese and Chinese descent. We re-sequenced all exons, selected intronic sequences and the promoter region in 24 individuals from our cohort. Fourteen SNPs were discovered, and six of these spanning 78 kb were genotyped in 1553 individuals from 672 families. All six SNPs were in linkage disequilibrium, and we found strong association of common risk haplotypes with hypertension in Chinese and Japanese (P<0.0001). In addition, individual SNPs showed association to total plasma cholesterol, LDL-cholesterol and VLDL-cholesterol levels, as well as obesity measures (body mass index). This analysis supports that PTP-1ß affects plasma lipid levels, and may lead to obesity and hypertension in Japanese and Chinese. Given similar associations found in other populations to insulin resistance and diabetes, this gene may play a crucial role in the development of the characteristic metabolic changes seen in patients with the metabolic syndrome.
* To whom correspondence should be addressed at: Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. Tel: +1 4144564968; Fax: +1 4144566516; Email: molivier{at}mcw.edu
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