Piotr Ksiazek

Angiotensin II Type 1 Receptor Gene Polymorphism in End-Stage Renal Disease

The genes of the renin-angiotensin system (RAS) are involved in progression of renal failure. We examined the A1166C polymorphism at the angiotensin II type 1 (AT1R) locus in patients with end-stage renal disease (ESRD). The distribution of genotype and allele frequencies was compared in 430 dialysis patients and 260 healthy controls. DNA samples were amplified by the polymerase chain reaction (PCR) and amplification products were digested with BsuRI restriction enzyme. In the presence of cytosine (C) there is a restriction site for this enzyme, giving a fragment of 231 bp (C allele), whereas undigested 255 bp fragment indicates the presence of the A allele. The higher frequency of combined AC and CC genotypes was observed in the patient group than in controls (48.6 vs. 39.5%, p < 0.05). The average time from the onset of renal disease to ESRD in patients with C allele was significantly shorter than in those with AA genotype (6.3 vs. 13 years, p < 0.01). Positive family history of renal disease in patients with AC/CC genotype seems to increase this effect. Our results indicate that the presence of C allele of the AT1R locus polymorphism might be associated with faster deterioration of renal function.

Endothelial Nitric Oxide Synthase Gene Intron 4 Polymorphism in Type 2 Diabetes Mellitus

AbstractIntroduction: Endothelial nitric oxide synthase (ecNOS) is a key regulator of vascular nitric oxide production. Polymorphism in intron 4 of the ecNOS gene is implicated in cardiovascular and renal diseases. We investigated a potential involvement of this polymorphism in the development of type 2 diabetes mellitus and its renal complications. Methods: This preliminary study involved 410 individuals with type 2 diabetes and 330 healthy control subjects. From the diabetes group 178 patients had diabetic nephropathy. All subjects were genotyped for the ecNOS4 polymorphism by the polymerase chain reaction (PCR) followed by gel electrophoresis. Genotype and allele frequencies were compared between diabetes patients with and without nephropathy and the control group. All calculations were performed using the Statistical Package for the Social Sciences (SPSS, Inc., Chicago, IL, USA) for Windows 5.0. The chi-square test and Fisher’s exact test were used for case-control comparisons. The Kruskal-Wallis test was used for the comparison of subgroups of patients with diabetes. Results: The analysis revealed that patients with diabetes, regardless of their nephropathy status, were significantly different in genotype distribution and 4a allele frequencies compared with controls (p < 0.05). The frequency of aa genotype was 8.2% in diabetic patients without nephropathy, 8.4% with those with nephropathy and 1.2% in controls. The 4a allele showed a significant effect on diabetic nephropathy, with odds ratio of 2.24 (95% confidence interval 1.12–3.40). There were no significant differences in the 4a allele frequency between the normotensive and hypertensive patients with diabetes. Conclusion: Our results suggest that the ecNOS gene polymorphism can serve as a useful genetic marker of increased susceptibility to type 2 diabetes and its renal complications.

Association of the Human Bradykinin B2 Receptor Gene with Chronic Renal Failure

AbstractIntroduction: The kallikrein-kinin system plays an important role in blood pressure homeostasis and renal sodium regulation, and some studies have reported that the kinins have a protective effect against hypertension and the development of renal disease. The B2-bradykinin receptor (B2R) mediates the majority of physiological actions of bradykinin. We investigated the effect of the C181→T polymorphism in exon 2 of the B2R gene in patients with end-stage renal disease (ESRD). Methods: This study involved 790 patients with ESRD and 510 healthy controls. All participants were genotyped for the B2R C181→T polymorphism by PCR followed by digestion of a PCR product with TaqI restriction endonuclease. DNA fragments were separated by agarose gel electrophoresis. Genotype and allele frequencies were compared between the groups. All calculations were performed using SPSS® 5.0 for Windows®. Results:B2R genotype distribution in patients and controls was in accordance with Hardy-Weinberg equilibrium. The frequency of the T allele was higher in ESRD patients than in controls. The significant difference was observed in the age at onset of renal disease; for patients with the T allele the mean age at onset was 36.8 years, compared with 52.4 years for those carrying only the C allele (p < 0.001). The frequencies of the T allele and carrier genotypes were not associated with gender, presence of hypertension, or underlying kidney disease. Conclusion: Our results suggest that the B2R polymorphism has a potential role in the earlier development of chronic renal failure in susceptible individuals. We did not confirm the previously published reports that the B2R gene polymorphism has a protective role in the development of ESRD.

M-charts as a tool for quantifying metamorphopsia in age-related macular degeneration treated with the bevacizumab injections

BackgroundThis article is aimed to assess quantitatively metamorphopsia using M-charts in patients suffering from wet age-related macular degeneration (AMD) treated with the intravitreal bevacizumab injections and to compare the results with traditional Amsler grid and ocular coherence tomography (OCT).MethodsThirty-six patients diagnosed with wet AMD were examined one day before and one month after the intraocular injection of bevacizumab. Horizontal and vertical metamorphopsia scores using M-charts, distance visual acuity, Amsler test and OCT were performed at each visit. Additionally, 23 healthy subjects were examined as a control group.ResultsThe rate of metamorphopsia detection was 89% with M-charts and 69% with Amsler test. The horizontal metamorphopsia score improved in 22 patients, the vertical metamorphopsia score improved in 16 patients, the Amsler grid results improved in 6 patients, visual acuity improved in 17 patients. There was no correlation between the degree of metamorphopsia and the visual acuity or the central retinal thickness (CRT). The specificity of both the M-charts and Amsler grid was 100%.ConclusionsThe rate of metamorphopsia detection in wet AMD patients was better with M-charts than with Amsler grid. M-charts may be used in the assessment of efficacy of treatment with intravitreal bevacizumab injections as another outcome measure, moreover they can be used even at home for the self-assessment. M-charts provide additional information concerning the visual function, independent of the visual acuity, CRT and morphological changes in OCT.

Complement factor H gene polymorphism and risk of cardiovascular disease in end-stage renal disease patients

The main cause of increased mortality in end-stage renal disease (ESRD) is cardiovascular disease (CVD). Complement factor H (CFH) may affect risk of CVD. Our study investigates a role of CFH Y402H polymorphism as a potential risk factor of CVD in a large group of patients. A group of 1200 patients with ESRD and 818 healthy controls were genotyped for the Y402H (T1277C) polymorphism. There was a significant difference in genotype frequencies between patients with CVD and those without CVD and healthy controls (p<0.001). Homozygosity for the C allele in CVD patients was associated with an odds ratio of 7.28 (95 % CI 5.32-9.95). No significant difference was found between patients without CVD and controls. Multivariate logistic regression analysis showed that Y402H genotype was independently associated with cardiovascular comorbidity in ESRD patients. This is the first study suggesting an association between CFH gene polymorphism and susceptibility to CVD in dialyzed patients.

Norepinephrine Transporter Gene (NET) Polymorphism in Patients with Type 2 Diabetes

Background: Norepinephrine transporter (NET) is involved in the regulation of norepinephrine (NE) turnover and metabolism. Neuronal NE reuptake may be impaired in individuals with renal disease and/or hypertension due to dysfunction of the NE transporter. A silent G1287A nucleotide substitution in exon 9 of the NET gene was studied in human conditions involving hypertension. We investigated its effect in patients with type 2 diabetes. Methods: The study involved 215 type 2 diabetes patients with nephropathy, 95 patients with diabetes duration ≧10 years, free of nephropathy, and 360 healthy subjects. All individuals were genotyped for the NET-8 gene polymorphism with the PCR-RFLP method. Genotype and allele frequencies were compared between the groups. NE was measured by high-performance liquid chromatography and electrochemical detection. Results: We genotyped 310 patients and 360 controls for the NET gene polymorphism. Genotype distribution in both groups was in accordance with the Hardy-Weinberg equilibrium. There were no significant differences in the frequency of genotypes and alleles between patients and controls (p = 0.43). The frequencies were also similar for patients with nephropathy and those without. After dividing the patient group into hypertensive (n = 208) and normotensive (n = 102) subjects, there was a significant increase in the frequency of the AA genotype in patients with hypertension compared to normotensives (19 vs. 10%, p < 0.05). Conclusion: No association was found between G1287A polymorphism in the NET gene and diabetes. Our results suggest that this polymorphism has a possible role in increased susceptibility to hypertension in patients with type 2 diabetes.

Cerebrospinal fluid biomarkers of β-amyloid metabolism and neuronal damage in epileptic seizures.

The main objectives of this study were to investigate if epileptic seizures have effects on brain metabolism of β‐amyloid (Aβ), as reflected by cerebrospinal fluid (CSF) levels of different isoforms of Aβ peptides and soluble amyloid precursor protein (APP), and neuronal degeneration, as reflected by CSF biomarker signs of acute neuronal injury.

Complement receptor 1 gene polymorphism and cardiovascular disease in dialyzed end-stage renal disease patients.

Inflammation plays an important role in cardiovascular disease (CVD). The complement system is a critical component of innate and acquired immunity. We investigated whether the polymorphisms in the complement receptor 1 (CR1) gene are associated with CVD in end-stage renal disease (ESRD) patients. The study groups of 1200 patients with ESRD, 360 patients with type 2 diabetes and 924 healthy individuals were genotyped. The GG genotype of the C5507G polymorphism was significantly more frequent in ESRD patients with CVD than in patients without CVD and controls (odds ratio [OR] = 3.44, 95% confidence interval [CI] = 2.23-5.3, and OR = 5.46, 95% CI = 3.72-8.0, respectively). The GG genotype was observed in 62% of patients with a history of myocardial infarction. The frequency of the G allele was also higher in patients with CVD (OR = 2.24, 95% CI = 1.93-2.61 vs controls, and OR = 1.97, 95% CI = 1.63-2.36 vs patients without CVD). In the multivariate logistic regression analysis the carrier status of G allele of C5507G polymorphism was an independent risk factor of CVD in ESRD patients (p < 0.001). In conclusion, our results suggest strong association between the CR1 gene polymorphism and CVD in ESRD patients.

Semi-automated kinetic perimetry provides additional information to static automated perimetry in the assessment of the remaining visual field in end-stage glaucoma

To test the hypothesis whether semi‐automated kinetic perimetry (SKP) provides additional information to static automated perimetry (SAP) in the assessment of the remaining visual field in end‐stage glaucoma, as defined by disc appearance (cup‐to‐disc ratio worse than 0.9) and SAP criteria (MD worse than 20 dB).