Dataset Information

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 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.

SUBMITTER: Chang TJ

PROVIDER: S-EPMC4998882 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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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 TJ Wang Wen-Chang WC Hsiung Chao A CA He Chih-Tsueng CT Lin Ming-Wei MW Sheu Wayne Huey-Herng WH Chang Yi-Cheng YC Quertermous Tom T Chen Ida I Rotter Jerome J Chuang Lee-Ming LM

Medicine 20160301 10

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 sus ...[more]

PMID: 26962801

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Project description:BackgroundWithdrawing medications that interfere with blood pressure (BP) is recommended in patients with uncontrolled BP, yet real-world use of such agents is not well characterized among individuals with hypertension. We aimed to evaluate the use of BP-interfering prescription medications among US patients with hypertension.MethodsThis retrospective drug utilization study used medical and prescription claims (January 2008 to December 2014) in the MarketScan commercial claims database. We included adults, aged 18-65 years, with a hypertension diagnosis (International Classification of Diseases, Ninth Revision, code 401) and ≥1 antihypertensive medication fill. Two hypertension cohorts were examined-new antihypertensive drug users (incident hypertension) and patients requiring titration to a fourth antihypertensive (incident treatment-resistant hypertension [TRH]). Patient-level exposure to BP-interfering medications was assessed 6 months before and after the index date, defined as the first prescription fill of an antihypertensive drug or the first occurrence of overlapping use of ≥4 antihypertensive drugs.ResultsWe identified 521,028 patients with incident hypertension and 131,764 patients with incident TRH. The most prevalent BP-interfering prescription medications were nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophens, and hormones. Overall, 18.3% of the incident hypertension cohort and 17.6% of the incident TRH cohort initiated a BP-interfering medication following antihypertensive titration. Among patients previously taking a BP-interfering medication, 57.6% with incident hypertension and 64.9% with incident TRH refilled that medication after antihypertensive intensification.ConclusionsThe use of prescription BP-interfering medications, especially NSAIDs, is prevalent among patients requiring intensification of their antihypertensive regimen. Greater efforts to limit the use of these medications, where feasible, may be required among patients with uncontrolled hypertension.

Project description:ObjectiveTo study whether treatment recommendations based on age and ethnicity according to United Kingdom (UK) clinical guidelines for hypertension translate to blood pressure reductions in current routine clinical care.DesignObservational cohort study.SettingUK primary care, from 1 January 2007 to 31 December 2017.ParticipantsNew users of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), calcium channel blockers (CCB), and thiazides.Main outcome measuresChange in systolic blood pressure in new users of ACEI/ARB versus CCB, stratified by age (< v ≥55) and ethnicity (black v non-black), from baseline to 12, 26, and 52 week follow-up. Secondary analyses included comparisons of new users of CCB with those of thiazides. A negative outcome (herpes zoster) was used to detect residual confounding and a series of positive outcomes (expected drug effects) was used to determine whether the study design could identify expected associations.ResultsDuring one year of follow-up, 87 440 new users of ACEI/ARB, 67 274 new users of CCB, and 22 040 new users of thiazides were included (median 4 (interquartile range 2-6) blood pressure measurements per user). For non-black people who did not have diabetes and who were younger than 55, CCB use was associated with a larger reduction in systolic blood pressure of 1.69 mm Hg (99% confidence interval -2.52 to -0.86) relative to ACEI/ARB use at 12 weeks, and a reduction of 0.40 mm Hg (-0.98 to 0.18) in those aged 55 and older. In subgroup analyses using six finer age categories of non-black people who did not have diabetes, CCB use versus ACEI/ARB use was associated with a larger reduction in systolic blood pressure only in people aged 75 and older. Among people who did not have diabetes, systolic blood pressure decreased more with CCB use than with ACEI/ARB use in black people (reduction difference 2.15 mm Hg (-6.17 to 1.87)); the corresponding reduction difference was 0.98 mm Hg (-1.49 to -0.47) in non-black people.ConclusionsSimilar reductions in blood pressure were found to be associated with new use of CCB as with new use of ACEI/ARB in non-black people who did not have diabetes, both in those who were aged younger than 55 and those aged 55 and older. For black people without diabetes, CCB new use was associated with numerically greater reductions in blood pressure than ACEI/ARB compared with non-black people without diabetes, but the confidence intervals were overlapping for the two groups. These results suggest that the current UK algorithmic approach to first line antihypertensive treatment might not lead to greater reductions in blood pressure. Specific indications could be considered in treatment recommendations.

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Dataset Information

Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension: A SAPPHIRe Cohort Study.

Publications

Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension: A SAPPHIRe Cohort Study.

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