TGF-β
            <sub>1</sub>
            DNA Polymorphisms, Protein Levels, and Blood Pressure

Li, Baogui; Khanna, Ashwani; Sharma, Vijay Kumar; Singh, Tejinder P.; Suthanthiran, Manikkam; August, Phyllis

doi:10.1161/01.hyp.33.1.271

Cited by 142 publications

(81 citation statements)

References 25 publications

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“…genotype at codon 25 is numerically higher in hypertensives compared with normotensives (19). Also, the reported allele frequencies at codon 10 permit appreciation of frequency differences between study populations by using a modest sample size.…”

Section: Increased Frequency Of Pro 10 Allele In Blacksmentioning

confidence: 87%

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Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

Suthanthiran

Li²,

Song³

et al. 2000

Proceedings of the National Academy of Sciences

192

128

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Hypertension, a remediable risk factor for stroke, cardiovascular disease, and renal failure, affects 50 million individuals in the United States alone. African Americans (blacks) have a higher incidence and prevalence of hypertension and hypertension-associated target organ damage compared with Caucasian Americans (whites). Herein, we explored the hypotheses that transforming growth factor-␤1 (TGF-␤1) is hyperexpressed in hypertensives compared with normotensives and that TGF-␤1 overexpression is more frequent in blacks compared with whites. These hypotheses were stimulated by our recent demonstration that TGF-␤1 is hyperexpressed in blacks with end-stage renal disease compared with white end-stage renal disease patients and by the biological attributes of TGF-␤1, which include induction of endothelin-1 expression, stimulation of renin release, and promotion of vascular and renal disease when TGF-␤ 1 is produced in excess. TGF-␤1 profiles were determined in black and white hypertensive subjects and normotensive controls and included circulating protein concentrations, mRNA steady-state levels, and codon 10 genotype. Our investigation demonstrated that TGF-␤1 protein levels are highest in black hypertensives, and TGF-␤1 protein as well as TGF-␤1 mRNA levels are higher in hypertensives compared with normotensives. The proline allele at codon 10 (Pro 10 ) was more frequent in blacks compared with whites, and its presence was associated with higher levels of TGF-␤1 mRNA and protein. Our findings support the idea that TGF-␤ 1 hyperexpression is a risk factor for hypertension and hypertensive complications and provides a mechanism for the excess burden of hypertension in blacks.

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Section: Increased Frequency Of Pro 10 Allele In Blacksmentioning

confidence: 87%

“…We have demonstrated that circulating levels of TGF-␤ 1 are higher in blacks with ESRD compared with white ESRD patients and that TGF-␤ 1 levels are also correlates of blood pressure in patients with ESRD (18,19). We hypothesized that the increased frequency of hyperexpression of TGF-␤ 1 may contribute to the excess burden of ESRD in blacks.…”

mentioning

confidence: 99%

Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

Suthanthiran

Li²,

Song³

et al. 2000

Proceedings of the National Academy of Sciences

192

128

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“…Seven polymorphisms in the TGF-βl gene have been reported in many studies. [8] In our study population, there is no correlation between TGF-βl gene polymorphisms and longitudinal change in peritoneal transport. It is unlikely to be a result of inadequate power, as median duration of dialysis was not long enough and it has a relatively small sample size.…”

Section: Discussionmentioning

confidence: 58%

“…We cannot confirm the effects of codon 10 and 25 polymorphism of TGF-β1 gene on the production of TGF-β1 protein. [8,22] It might be that the increased TGF-βl expression by MCs induced by high glucose or inflammatory state play an important role in peritoneal fibrosis and loss of function as an ultrafiltration barrier in chronic PD patients. [4,11] There are two important limitations in this study: a lack of the peritoneal biopsy that evaluated peritoneal fibrosis, and a lack of the results of plasma TGF-β1 levels.…”

Section: Discussionmentioning

confidence: 99%

“…Seven polymorphisms in the TGF-βl gene have been reported in a great number of studies. [8] At present, the basis for increased TGF-βl production in humans is unknown; however, recent evidence suggests that genetic factors may have a significant role to play in the increased TGFβl production. [7] The rate of increase in TGF-βl production in response to different stimuli such as high glucose or inflammatory cytokines may be different in each patient.…”

Section: Introductionmentioning

confidence: 99%

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TGF-β1 Gene Polymorphisms and Peritoneal Equilibration Test Results in CAPD Patients

et al. 2008

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Plasma Proteomics of Exercise Blood Pressure and Incident Hypertension

Rao,

Keyes,

et al. 2024

JAMA Cardiol

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ImportanceBlood pressure response during acute exercise (exercise blood pressure [EBP]) is associated with the future risk of hypertension and cardiovascular disease (CVD). Biochemical characterization of EBP could inform disease biology and identify novel biomarkers of future hypertension.ObjectiveTo identify protein markers associated with EBP and test their association with incident hypertension.Design, Setting, and ParticipantsThis study assayed 4977 plasma proteins in 681 healthy participants (from 763 assessed) of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE; data collection from January 1993 to December 1997 and plasma proteomics from January 2019 to January 2020) Family Study at rest who underwent 2 cardiopulmonary exercise tests. Individuals were free of CVD at the time of recruitment. Individuals with resting SBP ≥160 mm Hg or DBP ≥100 mm Hg or taking antihypertensive drug therapy were excluded from the study. The association between resting plasma protein levels to both resting BP and EBP was evaluated. Proteins associated with EBP were analyzed for their association with incident hypertension in the Framingham Heart Study (FHS; n = 1177) and validated in the Jackson Heart Study (JHS; n = 772) and Multi-Ethnic Study of Atherosclerosis (MESA; n = 1367). Proteins associated with incident hypertension were tested for putative causal links in approximately 700 000 individuals using cis-protein quantitative loci mendelian randomization (cis-MR). Data were analyzed from January 2023 to January 2024.ExposuresPlasma proteins.Main Outcomes and MeasuresEBP was defined as the BP response during a fixed workload (50 W) on a cycle ergometer. Hypertension was defined as BP ≥140/90 mm Hg or taking antihypertensive medication.ResultsAmong the 681 participants in the HERITAGE Family Study, the mean (SD) age was 34 (13) years; 366 participants (54%) were female; 238 (35%) were self-reported Black and 443 (65%) were self-reported White. Proteomic profiling of EBP revealed 34 proteins that would not have otherwise been identified through profiling of resting BP alone. Transforming growth factor β receptor 3 (TGFBR3) and prostaglandin D2 synthase (PTGDS) had the strongest association with exercise systolic BP (SBP) and diastolic BP (DBP), respectively (TGFBR3: exercise SBP, β estimate, −3.39; 95% CI, −4.79 to −2.00; P = 2.33 × 10−6; PTGDS: exercise DBP β estimate, −2.50; 95% CI, −3.29 to −1.70; P = 1.18 × 10−9). In fully adjusted models, TGFBR3 was inversely associated with incident hypertension in FHS, JHS, and MESA (hazard ratio [HR]: FHS, 0.86; 95% CI, 0.75-0.97; P = .01; JHS, 0.87; 95% CI, 0.77-0.97; P = .02; MESA, 0.84; 95% CI, 0.71-0.98; P = .03; pooled cohort, 0.86; 95% CI, 0.79-0.92; P = 6 × 10−5). Using cis-MR, genetically predicted levels of TGFBR3 were associated with SBP, hypertension, and CVD events (SBP: β, −0.38; 95% CI, −0.64 to −0.11; P = .006; hypertension: odds ratio [OR], 0.99; 95% CI, 0.98-0.99; P &lt; .001; heart failure with hypertension: OR, 0.86; 95% CI, 0.77-0.97; P = .01; CVD: OR, 0.84; 95% CI, 0.77-0.92; P = 8 × 10−5; cerebrovascular events: OR, 0.77; 95% CI, 0.70-0.85; P = 5 × 10−7).Conclusions and RelevancePlasma proteomic profiling of EBP identified a novel protein, TGFBR3, which may protect against elevated BP and long-term CVD outcomes.

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TGF-β ₁ DNA Polymorphisms, Protein Levels, and Blood Pressure

Cited by 142 publications

References 25 publications

Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

TGF-β1 Gene Polymorphisms and Peritoneal Equilibration Test Results in CAPD Patients

Plasma Proteomics of Exercise Blood Pressure and Incident Hypertension

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TGF-β 1 DNA Polymorphisms, Protein Levels, and Blood Pressure

Cited by 142 publications

References 25 publications

Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

TGF-β1 Gene Polymorphisms and Peritoneal Equilibration Test Results in CAPD Patients

Plasma Proteomics of Exercise Blood Pressure and Incident Hypertension

Contact Info

Product

Resources

About

TGF-β ₁ DNA Polymorphisms, Protein Levels, and Blood Pressure