Single nucleotide polymorphisms in protein tyrosine phosphatase 1beta (PTPN1) are associated with essential hypertension and obesity.
Protein tyrosine phosphatase 1beta (PTP-1beta) 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-1beta 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.
Olivier
Michael
M
Stanford Human Genome Center, Stanford University School of Medicine, CA, USA. molivier@mcw.edu
Hsiung
Chao A
CA
Chuang
Lee-Ming
LM
Ho
Lo-Tone
LT
Ting
Chih-Tai
CT
Bustos
Valerie I
VI
Lee
Teresa M
TM
De Witte
Anniek
A
Chen
Yii-Der I
YD
Olshen
Richard
R
Rodriguez
Beatriz
B
Wen
Chi-Chung
CC
Cox
David R
DR
D000328:Adult; D044466:Asian People; D015992:Body Mass Index; D002681:China; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D040461:Gene Components; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D017422:Sequence Analysis, DNA
D002784:Cholesterol; D017027:Protein Tyrosine Phosphatases