Genetic variation in the human sorbs1 gene is associated with blood pressure regulation and age at onset of hypertension: A SAPPHIRE cohort study

Tien Jyun Chang, Wen Chang Wang, Chao A. Hsiung, Chih Tsueng He, Ming Wei Lin, Wayne Huey Herng Sheu, Yi Cheng Chang, Tom Quertermous, Ida Chen, Jerome Rotter, Lee Ming Chuang

研究成果: 雜誌貢獻文章

3 引文 (Scopus)

摘要

Essential hypertension is a complex disease involving multiple genetic and environmental factors. A human gene containing a sorbin homology domain and 3 SH3 domains in the C-terminal region, termed SORBS1, plays a significant role in insulin signaling. We previously found a significant association between the T228A polymorphism and insulin resistance, obesity, and type 2 diabetes. It has been hypothesized that a set of genes responsible for insulin resistance may be closely linked with genes susceptible to the development of hypertension. Identification of insulin resistance-related genetic factors may, therefore, enhance our understanding of essential hypertension. This study aimed to examine whether common SORBS1 genetic variations are associated with blood pressure and age at onset of hypertension in an ethnic Chinese cohort. We genotyped 9 common tagged single nucleotide polymorphisms of the SORBS1 gene in 1136 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. Blood pressure was measured upon enrolment. The associations of the SORBS1 single nucleotide polymorphisms with blood pressure and the presence of hypertension were analyzed with a generalized estimating equation model. We used the false-discovery rate measure Q value with a cutoff <0.1 to adjust for multiple comparisons. In the Cox regression analysis for hypertension-free survival, a robust sandwich variance estimator was used to deal with the withinfamily correlations with age at onset of hypertension. Gender, body mass index, and antihypertension medication were adjustment covariates in the Cox regression analysis. In this study, genetic variants of rs2281939 and rs2274490 were significantly associated with both systolic and diastolic blood pressure. A genetic variant of rs2274490 was also significantly associated with the presence of hypertension. Furthermore, genetic variants of rs2281939 and rs2274490 were associated with age at onset of hypertension after adjustment for gender, body mass index, and antihypertension medication. In conclusion, we provide evidence for an association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and age at onset of hypertension. The biological mechanism of genetic variation associated with blood pressure regulation needs further investigation. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
原文英語
文章編號e2970
期刊Medicine (United States)
95
發行號10
DOIs
出版狀態已發佈 - 三月 4 2016

指紋

Age of Onset
Cohort Studies
Blood Pressure
Hypertension
Genes
Insulin Resistance
Single Nucleotide Polymorphism
Body Mass Index
Regression Analysis
Social Adjustment
src Homology Domains
Type 2 Diabetes Mellitus
Obesity
Insulin
Survival
Health

ASJC Scopus subject areas

  • Medicine(all)

引用此文

Genetic variation in the human sorbs1 gene is associated with blood pressure regulation and age at onset of hypertension : A SAPPHIRE cohort study. / Chang, Tien Jyun; Wang, Wen Chang; Hsiung, Chao A.; He, Chih Tsueng; Lin, Ming Wei; Sheu, Wayne Huey Herng; Chang, Yi Cheng; Quertermous, Tom; Chen, Ida; Rotter, Jerome; Chuang, Lee Ming.

於: Medicine (United States), 卷 95, 編號 10, e2970, 04.03.2016.

研究成果: 雜誌貢獻文章

Chang, TJ, Wang, WC, Hsiung, CA, He, CT, Lin, MW, Sheu, WHH, Chang, YC, Quertermous, T, Chen, I, Rotter, J & Chuang, LM 2016, 'Genetic variation in the human sorbs1 gene is associated with blood pressure regulation and age at onset of hypertension: A SAPPHIRE cohort study', Medicine (United States), 卷 95, 編號 10, e2970. https://doi.org/10.1097/MD.0000000000002970
Chang, Tien Jyun ; Wang, Wen Chang ; Hsiung, Chao A. ; He, Chih Tsueng ; Lin, Ming Wei ; Sheu, Wayne Huey Herng ; Chang, Yi Cheng ; Quertermous, Tom ; Chen, Ida ; Rotter, Jerome ; Chuang, Lee Ming. / Genetic variation in the human sorbs1 gene is associated with blood pressure regulation and age at onset of hypertension : A SAPPHIRE cohort study. 於: Medicine (United States). 2016 ; 卷 95, 編號 10.
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title = "Genetic variation in the human sorbs1 gene is associated with blood pressure regulation and age at onset of hypertension: A SAPPHIRE cohort study",
abstract = "Essential hypertension is a complex disease involving multiple genetic and environmental factors. A human gene containing a sorbin homology domain and 3 SH3 domains in the C-terminal region, termed SORBS1, plays a significant role in insulin signaling. We previously found a significant association between the T228A polymorphism and insulin resistance, obesity, and type 2 diabetes. It has been hypothesized that a set of genes responsible for insulin resistance may be closely linked with genes susceptible to the development of hypertension. Identification of insulin resistance-related genetic factors may, therefore, enhance our understanding of essential hypertension. This study aimed to examine whether common SORBS1 genetic variations are associated with blood pressure and age at onset of hypertension in an ethnic Chinese cohort. We genotyped 9 common tagged single nucleotide polymorphisms of the SORBS1 gene in 1136 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study. Blood pressure was measured upon enrolment. The associations of the SORBS1 single nucleotide polymorphisms with blood pressure and the presence of hypertension were analyzed with a generalized estimating equation model. We used the false-discovery rate measure Q value with a cutoff <0.1 to adjust for multiple comparisons. In the Cox regression analysis for hypertension-free survival, a robust sandwich variance estimator was used to deal with the withinfamily correlations with age at onset of hypertension. Gender, body mass index, and antihypertension medication were adjustment covariates in the Cox regression analysis. In this study, genetic variants of rs2281939 and rs2274490 were significantly associated with both systolic and diastolic blood pressure. A genetic variant of rs2274490 was also significantly associated with the presence of hypertension. Furthermore, genetic variants of rs2281939 and rs2274490 were associated with age at onset of hypertension after adjustment for gender, body mass index, and antihypertension medication. In conclusion, we provide evidence for an association between common SORBS1 genetic variations and blood pressure, presence of hypertension, and age at onset of hypertension. The biological mechanism of genetic variation associated with blood pressure regulation needs further investigation. Copyright {\circledC} 2016 Wolters Kluwer Health, Inc. All rights reserved.",
author = "Chang, {Tien Jyun} and Wang, {Wen Chang} and Hsiung, {Chao A.} and He, {Chih Tsueng} and Lin, {Ming Wei} and Sheu, {Wayne Huey Herng} and Chang, {Yi Cheng} and Tom Quertermous and Ida Chen and Jerome Rotter and Chuang, {Lee Ming}",
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AU - Hsiung, Chao A.

AU - He, Chih Tsueng

AU - Lin, Ming Wei

AU - Sheu, Wayne Huey Herng

AU - Chang, Yi Cheng

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