Ismail Setyopranoto

Vascular Endothelial Growth Factor 936 C/T Gene Polymorphism in Indonesian Subjects with Diabetic Polyneuropathy

AIM: This study aimed to confirm the role of f VEGF gene 936 C/T polymorphism and Diabetic Polyneuropathy (DPN) in the Indonesian population as well as to investigate its relationship with VEGF-A level and the role of vascular risk factors. MATERIAL AND METHODS: This was a cross-sectional study involving 152 subjects. Clinical symptoms and signs of DPN were examined using DNE and DNS scoring followed by nerve conduction study. All subjects underwent anthropometric, clinical examination and laboratory procedures to obtain body mass index, HbA1C level, lipid profile, Polymorphism of +936 C/T VEGF gene (PCR-RFLP technique), and VEGF-A plasma level (ELISA). Statistical analysis using a t-test or Mann-Whitney was performed to assess continuous data and Chi-square for categorical data. Multivariate logistic regressions were also performed to determine the relationship between independent variables and DPN. RESULTS: Sixty-nine (45.4%) fulfilled the diagnostic criteria of DPN. There was a significant association between CT + TT genotype and DPN (OR 0.35 95%CI 0.16-0.79 p = 0.01). Multivariate logistic regression showed that plasma VEGF-A level (OR = 1.003; 95% CI = 1.000-1.007; p = 0.03), diabetes duration (OR = 1.108; 95% CI = 1.045-1.175; p = 0.001), and CT+TT genotype (OR = 0.347; 95%CI = 0.148-0.817; p = 0.013) were associated with DPN. Sub-group analysis on subjects with HbA1C level ≥7% showed that VEGF-A (OR = 1.011; 95%CI = (1.004-1.017; p = 0.03), diabetes duration (OR = 1.245; 95% CI = 1.117-1.388; p < 0.001), CT + TT genotype (OR = 0.259; 95%CI = 0.074-0.911p = 0.035), with an adition of HDL (OR = 0.916; 95% CI = 0.857-0.978; p = 0.009) were significant predictors of DPN while LDL (OR = 1.017; 95% CI = 1.000-1.035; p = 0.053) acted as modifying factor. CONCLUSION: It appeared that CT + TT genotype of VEGF +936 gene might act as a protecting factor for DPN while VEGF-A, diabetes duration, HDL, and LDL acted as risk factors especially on subjects with HbA1C level ≥ 7.

The role of ejection fraction to clinical outcome of acute ischemic stroke patients

Aims: The aim of the study was to determine the effect of left ventricular ejection fraction on clinical outcomes of acute ischemic stroke patients. Study Design: This study design was a prospective cohort observational study. Place and Duration of Study: This study was conducted at Stroke Unit, Neurology Ward, and Cardiology Ward at the Dr. Sardjito Hospital, Yogyakarta, Indonesia, between July and December 2016. Materials and Methods: Hospitalized acute ischemic stroke patients were recruited, with sample was taken by consecutive sampling until reaching amount fulfilling inclusion criterion was 62 persons. In this study, clinical outcomes were measured by National Institutes of Health Stroke Scale (NIHSS) scores as well as dependent variables and left ventricular ejection fraction as independent variables. Logistic regression analyses were performed to discover any potential independent variable that can influence the left ventricular ejection fraction role at the clinical outcomes with NIHSS scores. Results: Multivariate analyses revealed that several variables were significantly interacted with the influence of left ventricular ejection fraction at the clinical outcomes with NIHSS scores. These variables were the left ventricular ejection fraction <48% (95% confidence interval [CI]: 0.691–0.925; P = 0.001), left ventricular ejection fraction + low high-density lipoprotein (HDL) (95% CI: 0.73–0.949; P = 0,001), left ventricular ejection fraction + diabetes mellitus (DM) (95% CI: 0.799–0.962; P = 0,001), and left ventricular ejection fraction + low HDL + DM (95% CI: 0.841–0.98; P = 0,001). Conclusion: The influence of the lower left ventricular ejection fraction to clinical outcome of ischemic stroke patients has a worsening of neurological deficit outcome by considering the combination of several independent variables including the DM and low HDL.

The D allele of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with worse functional outcome of ischaemic stroke

ABSTRACT Purpose: Insertion/deletion polymorphism in ACE gene (ACE I/D) is known to be associated with the occurrence of ischaemic stroke through its effect on pathogenesis of atherosclerosis and hypertension. This study was aimed to examine the association between this polymorphism with functional outcome of ischaemic stroke. Method: This was a cross-sectional study. The subjects were patients with ischaemic stroke in a reference hospital in Yogyakarta, Indonesia. Data on demographic characteristics, stroke risk factors, comorbidities and stroke severity were assessed on admission. The functional outcome, Barthel index (BI), was assessed when the patients were discharged from the hospital. ACE I/D genotypes of the patients were identified by polymerase chain reaction (PCR). Result: In total, 61 patients were included. Of these, 38 patients (62.3%) had II polymorphism, 22 patients (36.1%) had ID polymorphism and 1 patient (1.6%) had DD polymorphism in the ACE gene. There were significant differences in the functional outcomes between patients without D allele (II polymorphisms) and patients with D allele (ID and DD polymorphism) (mean BI on discharge: 75 ± 23.57 and 60.65 ± 27.15, respectively; p = 0.034). Multiple linear regression model showed that the availability of D allele is an independent variable negatively associated with functional outcome as assessed by BI (β = −0.232, p = 0.024). Conclusion: This study showed that the D allele in ACE I/D polymorphism is associated with worse functional outcomes. This highlights the possibility of further research to improve functional outcomes of ischaemic stroke by inhibiting the ACE system.