Genomic profile of Parkinson's disease in Asians

Parkinson's Disease (PD) has witnessed an alarming rise in prevalence, highlighting the suboptimal nature of early diagnostic and therapeutic strategies. To address this issue, genetic testing has emerged as a potential avenue. In this comprehensive review, we have meticulously summarized the variants associated with PD in Asian populations. Our review reveals that these variants exert their influence on diverse biological pathways, encompassing the autophagy-lysosome pathway, cholesterol metabolism, circadian rhythm regulation, immune system response, and synaptic function. Conventionally, PD has been linked to other diseases; however, our findings shed light on a shared genetic susceptibility among these conditions, implying an underlying pathophysiological mechanism that unifies them. Moreover, it is noteworthy that these PD-associated variants can significantly impact drug responses during therapeutic interventions. This review not only provides a consolidated overview of the genetic variants associated with PD in Asian populations but also contributes novel insights into the intricate relationships between PD and other diseases by elucidating shared genetic components. These findings underscore the importance of personalized approaches in diagnosing and treating PD based on individual genetic profiles to optimize patient outcomes

LONG-TERM COVID-19 EFFECT TO ENDOTHELIAL DAMAGE TROUGH EXTRINSIC APOPTOSIS LED TO CARDIOVASCULAR DISEASE PROGRESSION: AN UPDATE REVIEW

Covid-19 can involve persistence, sequelae, and other medical complications that last weeks to months after initial recovery; these prolonged symptoms called as long-term covid-19 effect. Symptoms, signs, or abnormal clinical parameters persisting two or more weeks after Covid-19 onset that do not return to a healthy baseline can potentially be long-term effects of the disease. SARS-CoV-2 affects the cardiovascular system and causes conditions such as myocarditis, arrhythmias, and myocardial injury. Vascular damage from Covid-19 has been affected directly by the SARS-CoV-2 virus infection and indirectly by systemic inflammatory cytokine storm. This damage can be long-lasting and lead to various cardiovascular complications. Fas ligand (FasL) - Fas complex is a death factor that induces cell apoptosis. Fas and FasL have been detected in the endothelial wall, and it has been proposed that Fas-mediated apoptosis has a role in physiological and pathological cell turnover in the endothelial wall. High concentrations of inflammatory cytokines, such as cytokines storm induced by SARS-CoV-2 infection, are thought to increase the expression of FasL, which leads to an increase in the regulation of extrinsic apoptosis in endothelial cells leading to endothelial damage. This article summarises the current understanding of the long-term covid-19 effect on endothelial damage through extrinsic apoptosis Fas-FasL complex

Correlation Between Circulating Levels of Pro-Inflammatory Cytokines TNF-alpha and Vascular Calcification Inhibitor Matrix Gla Protein in Obese Men

BACKGROUND: Adult obesity is rapidly increasing in the world including Indonesia. Tumor necrosis factor α (TNF-α) was chronically elevated in obese adipose tissue. TNF-α, a pleiotropic cytokine and also a regulator of bone formation, may might represent an important link between obesity and vascular calcification. Elegant genetic studies in mice and human have highlighted the important roles for Matrix Gla Protein (MGP) as an inhibitor of vascular calcification. The aim of this study was to examine the correlation between circulating levels of pro-inflammatory cytokines TNF-α and vascular calcification inhibitor MGP in obese men.METHODS: This was an observational cross-sectional study including 40 central obese men (waist circumference ≥90 cm) aged 31-60 years old. Serum MGP and serum TNF-α concentrations were quantified by ELISA principle. Fasting plasma glucose was assessed using hexokinase methods, triglyceride by GPO-PAP methods, and creatinine by Jaffe methods. All assays were performed according to the manufacture instruction. Statistical analysis was performed with SPSS for windows ver 16. Univariate analysis were performed to analyze mean, maximum, minimum value and SD. Pearson correlation statistic were performed to determine the correlation between variables. Significance value were define as alpha level = 0.05 based on two-tailed tests.RESULTS: The cross-sectional study (n=40) showed that the advancing age was correlated with plasma TNF-α concentration (r=0.348; p=0.028). The mean concentration of TNF-α and MGP were 8.323 and 8.368, respectively. We found a significant negative correlation between TNF-α with MGP (r=-0.425; p=0.006) and a significant correlation between TNF-α and triglyceride (r=0.375; p=0.017).CONCLUSIONS: Circulating level of TNF-α was inversely correlated with MGP concentration in obese men. This finding suggested that high level TNF-α leads to low MGP concentration obese men, hence, limits inhibitory capacity in vascular calcification

Genetic Polymorphisms of Ischemic Stroke in Asians

The increasing incidence of ischemic stroke emphasizes the necessity for early detection and preventive stra- tegies. Diagnostic biomarkers currently available for ischemic stroke only become detectable shortly before the manifestation of stroke symptoms. Genetic variants associated with ischemic stroke offer a potential solution to address this diagnostic limitation. However, it is crucial to acknowledge that genetic variants cannot be modified in the same way as epigenetic changes. Nevertheless, individuals carrying risk or protective variants can modify their lifestyle to potentially influence the associated epigenetic factors. This study aims to summarize specific variants relevant to Asian populations that may aid in the early detection of ischemic stroke and explore their impact on the disease’s pathophysiology. These variants give us important information about the genes that play a role in ischemic stroke by affecting things like atherosclerosis pathway, blood coagulation pathway, homo- cysteine metabolism, transporter function, transcription, and the activity of neurons regulation. It is important to recognize the variations in genetic variants among different ethnicities and avoid generalizing the pathogenesis of ischemic stroke

Osteoprotegerin Serum Level is Associated with Severity of Coronary Artery Calcification in Non Diabetic Centrally Obese Men

BACKGROUND: Osteoprotegerin (OPG) is produced by a variety of tissues including those of the cardiovascular system. Recent clinical studies have suggested a significant correlation between elevated OPG serum level and cardiovascular mortality. Since coronary artery calcification (CAC) is positively associated with cardiovascular disease (CVD) events, we carried out a study to investigate whether OPG serum level is associated with the severity of CAC in non diabetic centrally obese men.METHODS: A cross sectional study was done on seventy non diabetic centrally obese men. CAC score was determined by using dual source computed tomography (DSCT). OPG serum level was measured by enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis was done with SPSS for windows ver 16. ANOVA was performed to analyze mean, maximum, minimum value, and standard deviation. Spearman correlation test was performed to determine the correlation between OPG serum level and CAC score. Significance value was defined as alpha level=0.05 based on two-tailed tests.RESULTS: OPG serum level was significantly correlated with CAC score. The severity of CAC increased with the increase of OPG level. Age was significantly correlated with OPG serum level and CAC score.CONCLUSIONS: Our data show that serum OPG level was associated with the severity of CAC, which highlights that OPG could be involved in the progression of CAC in non diabetic obese men.KEYWORDS: obesity, vascular calcification, osteoprotegerin, coronary artery calcificatio

The Apo gene's genetic variants: hidden role in Asian vascular risk

Vascular risk factors, including diabetes, hypertension, hyperlipidemia, and obesity, pose significant health threats with implications extending to neuropsychiatric disorders such as stroke and Alzheimer's disease. The Asian population, in particular, appears to be disproportionately affected due to unique genetic predispositions, as well as epigenetic factors such as dietary patterns and lifestyle habits. Existing management strategies often fall short of addressing these specific needs, leading to greater challenges in prevention and treatment. This review highlights a significant gap in our understanding of the impact of genetic screening in the early detection and tailored treatment of vascular risk factors among the Asian population. Apolipoprotein, a key player in cholesterol metabolism, is primarily associated with dyslipidemia, yet emerging evidence suggests its involvement in conditions such as diabetes, hypertension, and obesity. While genetic variants of vascular risk are ethnic-dependent, current evidence indicates that epigenetics also exhibits ethnic specificity. Understanding the interplay between Apolipoprotein and genetics, particularly within diverse ethnic backgrounds, has the potential to refine risk stratification and enhance precision in management. For Caucasian carrying the APOA5 rs662799 C variant, pharmacological interventions are recommended, as dietary interventions may not be sufficient. In contrast, for Asian populations with the same genetic variant, dietary modifications are initially advised. Should dyslipidemia persist, the consideration of pharmaceutical agents such as statins is recommended

Correlation Between Systemic Arterial Hypertension and Bone Morphogenetic Protein-2 in Central Obese Non-Diabetic Men with Evidence of Coronary Artery Calcification

BACKGROUND: Previous studies have confirmed separately the relationship between obesity, insulin-resistance, hypertension and bone morphogenetic protein-2 (BMP-2) with coronary artery calcification, a parameter of subclinical atherosclerosis. It was also reported that BMPs may function as proinflammatory, prohypertensive and proatherogenic mediators. The study aimed to assess the correlation between systemic hypertension and BMP-2 plasma concentration in central-obese non-diabetic men with evidence of coronary artery calcification.METHODS: This was a cross sectional study on 60 central-obese non-diabetic men, of an average age of 55.2 years, with evidence of coronary calcification, who came for health check-up and met the inclusion criteria consecutively as defined by waist circumference >90 cm and fasting blood glucose <126 mg/dL. Coronary calcification was defined by coronary artery calcium (CAC) score ≥10 Agatson-unit Dual Source 64 slice CT scan.RESULTS: There is positive correlation between hypertension and BMP-2 in central-obese non-diabetic men with evidence of coronary artery calcification. BMP-2 plasma concentration was higher in the hypertensive subjects. The correlation was stronger in younger (<55 years old) subjects and subjects with insulin-resitance