Genetic Basis for Increased Risk for Vascular Diseases in Diabetes

Author(s):  
Dwaipayan Bharadwaj ◽  
Anjali Singh
2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Germán D. Carrasquilla ◽  
Malene Revsbech Christiansen ◽  
Tuomas O. Kilpeläinen

Abstract Purpose of Review Hypertriglyceridemia is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. Severe hypertriglyceridemia may sometimes be a monogenic condition. However, in the vast majority of patients, hypertriglyceridemia is due to the cumulative effect of multiple genetic risk variants along with lifestyle factors, medications, and disease conditions that elevate triglyceride levels. In this review, we will summarize recent progress in the understanding of the genetic basis of hypertriglyceridemia. Recent Findings More than 300 genetic loci have been identified for association with triglyceride levels in large genome-wide association studies. Studies combining the loci into polygenic scores have demonstrated that some hypertriglyceridemia phenotypes previously attributed to monogenic inheritance have a polygenic basis. The new genetic discoveries have opened avenues for the development of more effective triglyceride-lowering treatments and raised interest towards genetic screening and tailored treatments against hypertriglyceridemia. Summary The discovery of multiple genetic loci associated with elevated triglyceride levels has led to improved understanding of the genetic basis of hypertriglyceridemia and opened new translational opportunities.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Günter Siegel ◽  
Eugeny Ermilov

Background: ALP and GGT are indispensable constituents of brain microvessel endothelial cells, expressed and induced by IL-6. High values are entangled in affecting blood-brain barrier functionality. Since SOD bound to brain basement membrane and matrix heparan sulfate proteoglycan, is implicated in β-amyloid efflux, we examined in a pilot study of 11 patients with metabolic syndrome (MS) whether these biomarkers can be beneficially influenced through an antioxidant phytochemical approach with Ginkgo biloba (EGb 761, 2 × 120 mg/d). Also, MS is associated with an increased risk of developing diabetes and cardio-cerebro-vascular diseases (CCVD) (Figure). Methods: Photometric methods, ELISAs, EIAs and laser ellipsometry were applied. Results: A 2-month medication led to brain/liver biomarker changes: ALP -14.8% (p < 0.004), GGT -11.3% (p < 0.010). Antioxidative biomarker changes: SOD +17.7% (p < 0.009), GPx +11.6% (p <0.001), oxLDL/LDL -21.0% (p < 0.002), 8- iso -PGF 2α -39.8% (p < 0.003), MPO -29.6% (p < 0.014). Antiinflammatory biomarker changes: IL-6 -12.9% (p < 0.041), Lp(a) -26.3% (< 0.001), hs-CRP -39.3% (< 0.005), WBC -6.3% (< 0.023), MMP-9 -32.9% (< 0.042). Vasodilator biomarker changes: cAMP +43.5% (< 0.001), cGMP +32.9% (< 0.001), nanoplaque formation -14.3% (p < 0.008), nanoplaque size -23.4% (p < 0.0004). Conclusion: Since under ginkgo ALP and GGT were downregulated and SOD upregulated, and plasma biomarkers of oxidative stress, plaque stability and progression, inflammation, vasodilatory second messengers and lipid composition beneficially altered, this phytochemical may be estimated as complementary drug with potentially preventive character for CCVD.


2013 ◽  
pp. 220-226
Author(s):  
Chiara Trenti ◽  
Emanuele A. Negri ◽  
Ido Iori ◽  
Davide Favali

Background: Hypertriglyceridemia is a common biochemical finding. Depending on the triglyceride levels it can be associated with increased risk of acute pancreatitis and of cardiovascular disease. The most severe forms have a genetic basis. Clinical case: We report a case of a 60-year-old woman with very high triglycerides (800- 3,000 mg/dL) and normal cholesterol levels. The patient is a non smoker, on hypolipemic diet, non alcoholic consumer, and on regular physical exercise. Her blood pressure is normal, BMI is 20, waist circumference is 78 cm. Thyroid, renal and hepatic function are normal. She has never had acute pancreatitis or cardiovascular disease. Discussion: The diagnostic and therapeutic management of this case is discussed. Causes of primary (genetic) and secondary hypertriglyceridemia are also reviewed, together with clinical features and management on every day practice. We focused on severe hypertriglyceridemia.


2005 ◽  
Vol 109 (4) ◽  
pp. 355-364 ◽  
Author(s):  
Shushant Jain ◽  
Nicholas W. Wood ◽  
Daniel G. Healy

Major progress has been made in the last decade in understanding the genetic basis of PD (Parkinson's disease) with five genes unequivocally associated with disease. As a result, multiple pathways have been implicated in the pathogenesis of PD, including proteasome impairment and mitochondrial dysfunction. Although Mendelian genetics has been successful in establishing a genetic predisposition for familial PD, this has not been reiterated in the sporadic form. In fact no genetic factors have been unequivocally associated with increased risk for sporadic PD. The difficulty in identifying susceptibility factors in PD has not only been because of numerous underpowered studies, but we have been unable to dissect out the genetic component in a multifactorial disease. This review aims to summarize the genetic findings within PD.


2016 ◽  
Vol 11 (2) ◽  
pp. 179-182 ◽  
Author(s):  
Naoki Nakaya ◽  
Tomohiro Nakamura ◽  
Naho Tsuchiya ◽  
Akira Narita ◽  
Ichiro Tsuji ◽  
...  

AbstractObjectiveThis study examined the association between psychological distress and the risk of withdrawing from hypertension treatment (HTTx) 1 year after the earthquake disaster in the coastal area affected by the Great East Japan Earthquake (GEJE).MethodsUsing cross-sectional data from 2012, we studied people over 20 years of age living in Shichigahama Town, Miyagi, on the northeastern coast of Japan, which had been severely inundated by the tsunami that followed the GEJE in 2011. A total of 1014 subjects were categorized as in need of HTTx. Withdrawing from HTTx was assessed by using a self-reported questionnaire.ResultsSubjects with a higher degree of psychological distress (Kessler-6 [K6] score ≥ 13) exhibited a significantly higher risk of withdrawing from HTTx, compared with subjects with a lower degree of psychological distress (K6 score ≤ 12; odds ratio=4.0; 95% confidence interval: 1.3-10.6, P<0.01).ConclusionsThis study indicated that psychological distress is a risk factor for withdrawing from HTTx in post-disaster settings. Our data suggested that the increased risk of withdrawing from HTTx associated with post-disaster psychological distress may underlie the increased prevalence of vascular diseases after the earthquake disaster in coastal areas affected by the tsunami. (Disaster Med Public Health Preparedness. 2017;11:179–182)


2019 ◽  
Vol 13 (3) ◽  
pp. 137-151 ◽  
Author(s):  
Rudy Celeghin ◽  
Gaetano Thiene ◽  
Barbara Bauce ◽  
Cristina Basso ◽  
Kalliopi Pilichou

Cardiovascular diseases (CVDs) are a wide group of disorders affecting the heart and blood vessels, including coronary artery, valve, pericardial, conduction system, myocardial and vascular diseases, either congenital or acquired, which can be also heritable. The advent of next generation sequencing (NGS) was accompanied by quick advances in understanding the genetic basis of human diseases, prompting translation of genetics to the clinic. Precision medicine is based on these findings and on the role of genetic testing to improve the diagnosis, to identify individuals with previously unrecognized disease and family members at risk of future disease development which require longitudinal follow-up. However, the probabilistic nature of genetic testing and the subjectivity of genetic variants classification weighted on current evidence, making this powerful clinical tool difficult to be applied in precision diagnostics and therapeutics. Here, we reviewed systematically the genetic basis of CVDs with special emphasis on the current role of NGS in clinical diagnosis and risk assessment, underlying the need of multidisciplinary cardio-genetic referral centers.


2010 ◽  
Vol 103 (04) ◽  
pp. 749-756 ◽  
Author(s):  
Francesca Cesari ◽  
Rosanna Abbate ◽  
Franco Gensini ◽  
George Broze ◽  
Sandra Fedi ◽  
...  

SummaryThe relationship between protein Z levels and thrombosis is controversial. We performed a systematic review and meta-analysis of the available studies to assess the association between protein Z and vascular thrombotic diseases. We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library, bibliographies of retrieved articles and abstracts of congresses up to October, 2009. Studies were included if they analysed protein Z levels in patients with vascular thrombotic diseases. After the review process, 28 case-control studies (33 patient cohorts), including 4,218 patients with thrombotic diseases and 4,778 controls, were selected for analysis. The overall analysis using a random-effects model showed that low protein Z levels were associated with an increased risk of thrombosis (odds ratio [OR] 2.90, 95% confidence interval [CI] 2.05–4.12; p<0.00001). On subgroup analysis, a significant association was found between low protein Z levels and arterial vascular diseases (OR 2.67, 95%CI 1.60–4.48; p=0.0002), pregnancy complications (OR 4.17, 95%CI 2.31–7.52; p<0.00001), and venous thromboembolic diseases (OR 2.18, 95%CI 1.19–4.00; p=0.01). The results of this meta-analysis are consistent with a role for protein Z deficiency in thrombotic diseases, including arterial thrombosis, pregnancy complications and venous thromboembolism.


2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Luis Rodríguez-Rodríguez ◽  
Raquel López-Mejías ◽  
Mercedes García-Bermúdez ◽  
Carlos González-Juanatey ◽  
Miguel A. González-Gay ◽  
...  

Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between theHLA-DRB1*04shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G>A, rs1800629) of theTNFAlocus, the rs1801131 polymorphism (A>C; position + 1298) of theMTHFRlocus, or a deletion of 32 base pairs on theCCR5gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA.


2011 ◽  
Vol 19 (4) ◽  
pp. 864-873 ◽  
Author(s):  
Jan Westerink ◽  
Yolanda van der Graaf ◽  
Daniël R Faber ◽  
Wilko Spiering ◽  
Frank LJ Visseren

Aims: To investigate whether levels of thyroid-stimulating hormone (TSH) within the normal range are associated with an increased risk of new vascular events and mortality in patients with clinical manifest vascular diseases and whether this relation is influenced by adiposity. Methods and results: Prospective cohort study in 2443 patients (1790 men and 653 women) with clinical manifest vascular disease and TSH levels in the normal range. Median follow up was 2.7 (interquartile range 1.4–3.9) years. Clinical endpoints of interest were: myocardial infarction, stroke, vascular death, and all-cause mortality. In patients with manifest vascular disease, the prevalence of (subclinical) hypothyroidism was 5.7%, while 3.6% had (subclinical) hyperthyroidism. An increase in 1 unit of TSH was associated with a 33% higher risk (HR 1.33; 95% CI 1.03–1.73) for the occurrence of myocardial infarction, adjusted for age, gender, renal function, and smoking. In patients with a body mass index (BMI) below the median of 26.7 kg/m2 the HR per unit TSH for myocardial infarction was 1.55 (95% CI 1.08–2.21) compared to 1.18 (95% CI 0.81–1.71) in patients with a BMI ≥26.7 kg/m2. Visceral adipose tissue thickness below the median (≤8.8 cm) was associated with higher HR per unit TSH for myocardial infarction (HR 1.69; 95% CI 1.21–2.35) compared to visceral adipose tissue thickness >8.9 cm (HR 1.00; 95% CI 0.66–1.49). There was no relation between TSH and risk of stroke, vascular death, the combined endpoint, or all-cause mortality. Conclusion: Higher TSH levels within the normal range are associated with an increased risk of myocardial infarction, in patients with clinical manifest vascular disease. This relation is most prominent in patients without visceral obesity.


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