https://scholars.lib.ntu.edu.tw/handle/123456789/627699
標題: | Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension: A SAPPHIRe Cohort Study | 作者: | TIEN-JYUN CHANG Wang, Wen-Chang Hsiung, Chao A He, Chih-Tsueng Lin, Ming-Wei Sheu, Wayne Huey-Herng YI-CHENG CHANG Quertermous, Tom Chen, Ida Rotter, Jerome LEE-MING CHUANG |
關鍵字: | GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; MOLECULAR-GENETICS; METABOLIC SYNDROME; LOCI; POLYMORPHISM; VARIANTS; OBESITY; RISK | 公開日期: | 三月-2016 | 出版社: | LIPPINCOTT WILLIAMS & WILKINS | 卷: | 95 | 期: | 10 | 來源出版物: | Medicine | 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 within-family 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627699 | ISSN: | 0025-7974 | DOI: | 10.1097/MD.0000000000002970 |
顯示於: | 醫學系 |
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