Association of OSR-1 With Vascular Dysfunction and Hypertension in Polycystic Kidney Disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is associated with oxidative stress and hypertension development before renal function decline and cardiovascular disease development. Oxidative stress-responsive kinase-1 (OSR-1) participates in the signaling regulating Na+ transport during oxidative stress and also plays a role in the regulation of cell volume and blood pressure. Therefore, we aimed to investigate the potential role of OSR-1 in ADPKD patients. Eighty ADPKD patients, 80 healthy controls, and 80 non-ADPKD patients with hypertension were enrolled in this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood samples were taken after 12-h fasting for the measurement of biochemical parameters and OSR-1 gene expression. Vascular dysfunction was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). Briefly, of the 80 ADPKD patients, 41(51%) were male, and 53(66%) of them were hypertensive. The mean age of the 80 controls was 35.3 ± 12.6 years, and 37(46%) of them were male. The mean age of the 80 non-ADPKD patients with hypertension was 44.6 ± 11.9 years, and 38(47.5) of them were male. There were significant differences in serum OSR-1 gene expression between the ADPKD patients and the control subjects. Serum OSR-1 gene expression was also significantly increased in hypertensive ADPKD patients in comparison with both normotensive ADPKD counterparts and non-ADPKD hypertensive subjects. Serum OSR-1 gene expression was increased in patients with ADPKD than healthy subjects. Low estimated glomerular filtration rate (eGFR), OSR-1 gene expression, total kidney volume (TKV), and high-density lipoprotein (HDL) were also independently associated with hypertension in ADPKD patients.

The Association of Brain-Derived Neurotrophic Factor Gene Polymorphism with Obstructive Sleep Apnea Syndrome and Obesity.

BACKGROUND: Obesity represents a major risk factor for Obstructive Sleep Apnea Syndrome (OSAS). Brain-derived neurotrophic factor (BDNF) affects the mechanisms that regulate weight, eating behavior, and metabolism. This project aims to investigate the possible association of BDNF gene polymorphism with obesity and OSAS, and to contribute knowledge to the understanding of the pathophysiology of OSAS. METHODS: The subjects included in this study were selected among the individuals who were hospitalized in the Erciyes University Medical School Chest Diseases Sleep Medicine Laboratory. Subjects were divided into four groups based on the presence of OSAS and/or obesity. Group 1 included OSAS+ obesity+ patients, Group 2 included OSAS+ obesity- patients, Group 3 included OSAS- obesity+ patients, and Group 4 included OSAS- obesity- patients. The targeted patient number per each study group was 45, but only 32 patients could be enrolled into Group 3. RESULTS: Out of a total number of 167 subjects, 117 (70.1 %) had BDNF 196G/G, 48 (28.7 %) had BDNF 196G/A, and 2 (1.2 %) had BDNF 196A/A genotype. Of 48 subjects having BDNF 196G/A genotype, 32 (66.6 %) were obese, and 16 (33.3 %) were non-obese. Out of 90 subjects with OSAS, 64 (71.1 %) had BDNF 196G/G, and 25 (27.8 %) had BDNF 196G/A genotype. Out of 77 subjects without OSAS, BDNF 196G/G, and BDNF 196G/A genotypes were detected in 53 (68.8 %) and 23 (29.9 %) subjects, respectively. A statistically significant difference was demonstrated between the four study groups in terms of BDNF rs6265 polymorphism (p = 0.013). This difference was attributed to OSAS+ obesity- Group, in which BDNF 196G/G genotype was more common and BDNF 196G/A polymorphism was less common than the patients in other groups. CONCLUSION: In conclusion, BDNF 196G/A genotype was found to be more frequent among obese patients compared to the non-obese individuals, but it was not significantly related to OSAS in the present study. BDNF196G/G genotype was more common and BDNF 196G/A polymorphism was less common among OSAS+ obesity- subjects compared to the other study groups.

Characterization of the Interleukin-28B Gene rs12979860 C/T Polymorphism in Turkish Chronic Hepatitis C Patients and Healthy Individuals.

BACKGROUND: Host genetic factors can affect the progress of hepatitis-C virus (HCV) infection. Interleukin-28B (IL28B) single nucleotide polymorphisms may play an important role in the clearance of HCV spontaneously or with treatment. AIMS: The aim of our study was to evaluate the rate of IL28B genotypes in patients with Chronic Hepatitis-C (CHC) and healthy control subjects and to examine the characteristics of patients in each IL28B subgroup. STUDY DESIGN: Case-control study. METHODS: IL28B polymorphisms were genotyped by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) in all subjects. RESULTS: The mean age was 52.3±10.9 years (33% female) in the CHC patients and 52.5±11.5 years (39.1% female) in the healthy controls. The percentage of patients with a high baseline viral load (≥400,000 IU/mL) was higher in the CT group (69.8%) compared to the C/C (44.4%) and T/T (50%) groups (p=0.021). There was no significant difference in liver fibrosis and liver necroinflammation distribution among the CC, CT and TT genotypes with mild, moderate and severe groups (p=0.058 and p=0.791, respectively). Mean age, gender ratio, body mass index, viral load at baseline, rate of HCV genotypes, baseline ALT levels were not significantly different among the three IL28B subgroups (p>0.05). A significant increase was observed in the frequencies of IL28B rs12979860 TT genotypes in the CHC patients (20.6%) compared to the healthy control group (8.7%) (p=0.033). CONCLUSION: In the patients with chronic HCV-genotype 1b and 4 infections, the IL28B rs12979860 (C>T) gene polymorphism frequency of the TT genotype and T allele was higher than in healthy control subjects. This result indicates that the TT genotype may be more effective in the progression of HCV infection than other genotypes.

Association of TNF-α -308 G > A and ACE I/D gene polymorphisms in hemodialysis patients with arteriovenous fistula thrombosis.

PURPOSE: Tumor necrosis factor-α (TNF - α) -308 G > A promoter polymorphism seems to be associated with adverse clinical outcome in hemodialysis patients (HD). Angiotensin-converting enzyme (ACE) gene may be the causative factor contributing to the deterioration of renal functions. The aim of this study was to investigate the relationship between vascular access failure and the genetic polymorphisms of ACE and TNF-α gene. METHODS: We enrolled and genotyped 47 HD patients with arteriovenous fistula (AVF) thrombosis, 51 HD patients without AVF thrombosis, and 40 healthy controls. The genotypes of these polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotype distribution of TNF-α -308 G > A in patients with thrombosis was significantly different from the patients without thrombosis (p = 0.008). There was no significant difference between the two groups in terms of ACE I/D polymorphism (p = 0.213). CONCLUSION: Our results propose that TNF-α -308 G > A genotype may be a potential genetic marker on HD patients with AVF thrombosis.