Gulen Attila

Effects of apolipoprotein E genotypes and other risk factors on the development of coronary artery disease in Southern Turkey.

BACKGROUND Apolipoprotein E (apoE) plays a major role in lipoprotein metabolism and lipid transport. Associations between apoE genotypes, coronary artery disease (CAD) and other risk factors have been described by many investigators. The aim of this study was to investigate the role of apoE gene polymorphism and other risk factors in the development of CAD in subjects whose coronary arteries were evaluated by means of coronary angiography. METHODS The study population consisted of 199 subjects (114 male and 55 female). Of the total, 107 had CAD. The apoE gene was amplified by polymerase chain reaction (PCR) and then digested by CfoI restriction enzyme. The plasma lipid levels and other risk factors were also determined in all subjects. RESULTS The epsilon2 and epsilon4 allele frequencies and genotypes carrying epsilon4 allele were significantly higher in CAD (+) patients. Plasma lipids except triglycerides were increased in CAD (+) cases. We found that apoE genotypes, HT, DM, male gender, age and smoking were the independent predictors of CAD. There was no association between apoE alleles and lipids. CONCLUSION We conclude that apoE polymorphism (presence of epsilon4 allele) is associated with the development of CAD in Southern Turkey. In our study, we did not observe any effect of apoE alleles on lipid levels.

Apolipoprotein E polymorphism in childhood nephrotic syndrome.

Abstract Recent clinical reports have demonstrated that the progression and prognosis of renal diseases are possibly influenced by apolipoprotein E (apoE) genotypes and alleles. In this study we investigated whether apoE genotypes and alleles can be a prognostic criterion for the steroid responsiveness in childhood nephrotic syndrome. One hundred and seven pediatric patients with primary idiopathic nephrotic syndrome and 83 healthy volunteers were enrolled in the study. Eighty-seven of the patients had steroid-sensitive nephrotic syndrome (SSNS) and 20 had steroid-resistant nephrotic syndrome (SRNS). The ɛ2 allele frequency and ɛ2/3 genotype frequency of the SNRS group were statistically higher when compared with SSNS and control groups (P<0.05). The higher frequency of the ɛ2 allele in steroid resistant nephrotic patients suggests that the ɛ2 allele gives a possible genetic predisposition to steroid resistance in our population, but further studies are needed to clarify this subject.

GENETIC HETEROGENEITY OF β-THALASSEMIA AT ÇUKUROVA IN SOUTHERN TURKEY

β-Thalassemia is the most common genetic abnormality causing health problems worldwide.Ç ukurova, in the southern part of Turkey, being on the Mediterranean, is in the thalassemic belt. Since there is no cure for the disease at present, the frequency of the mutation types of β-thalassemia must first be identified to aid in clinical follow-up and prenatal diagnosis. Carriers identified during a screening survey and patients referred to our laboratory were studied for this purpose. After routine hematological analysis molecular screening was performed by the amplification refractory mutation system and DNA sequencing. The frequency of the common mutations were: IVS-I-110 (G→A) 57.3%, IVS-I-1 (G→A) 8.3%, codon 39 (C→T) 6.4%, IVS-I-6 (T→C) 5.7%, frameshift codon 8 (–AA) 5.7%, –30 (T→A) 4.7%, IVS-II-1 (G→A) 3.4%, IVS-II-745 (G→C) 2.8%, and frameshift codon 5 (–CT) 1.1%. Some rare mutations (1%) such as frameshift codon 44 (–C) 0.7%, frameshift codons 74/75 (–C) 0.7%, IVS-I-5 (G→C) 0.7%, frameshift codons 8/9 (+G) 0.4%, frameshift codons 36/37 (–T) 0.4%, frameshift codons 22/23/24 (–AAGTTGG) 0.4%, IVS-I-130 (G→C) 0.4%, IVS-I-5 (G→T) 0.2%, –28 (A→C) 0.2%, codon 15 (TGG→TGA) 0.2%, and frameshift codons 82/83 (–G) 0.2%, were detected by sequence analysis. The codon 15 (TGG→TGA) and frameshift codons 82/83 (–G) mutations were seen in Turkey for the first time.

Endothelial nitric oxide synthase gene intron 4 a/b VNTR polymorphism in children with APSGN

The role of endothelial nitric oxide synthase gene intron 4 a/b (eNOS4a/b) variable number of tandem repeats (VNTR) polymorphism in various renal diseases was investigated. We investigated whether the eNOS4a/b VNTR polymorphism is associated with susceptibility to acute poststreptococcal glomerulonephritis (APSGN) and its clinical features. Endothelial NOS4a/b VNTR polymorphism is determined by the polymerase chain reaction in 60 children with APSGN, and 66 healthy controls. The genotype distribution of eNOS4 does not differ between the patients and the controls (X2=5.1, p=0.079). However, the frequency of eNOS4a (eNOS4a/a and eNOS4a/b) genotype is higher in the patients than in the controls (X2=4.5, p=0.046). In the APSGN group we performed renal biopsy on eight patients because of nephrotic syndrome accompanies acute nephritic syndrome or glomerular filtration rate (GFR) is lower than 50% of normal, and found that to carry a/a and a/b genotypes were a significant risk factor for this type presentation (OR=17.3, 95% CI:1.95-152.67, p=0.03). Mean serum creatinine values are found statistically significantly higher in a/a and a/b genotypes when compared with b/b genotypes (p=0.022). Children carrying the “aa” and “ab” genotype or “a” allele of eNOS4 have a greater tendency to develop and clinical presentation of APSGN.

Changes in osmolal gap and osmolality in children with chronic and end-stage renal failure.

within the reference range in patients with renal failure [6] . However, the role of OG and serum osmolality in this condition was not established very well. The aim of this study is to determine the serum OG and osmolality in children with various stages of CRF and the effect of dialysis modalities on these parameters. We also investigated the possible relationship among the changes of OG and serum osmolality before and after HD in patients with CRF. We studied 101 patients (52 boys and 49 girls), with known CRF. Thirty-six patients (age range 5–16 years) underwent HD (HD patients), 29 patients peritoneal dialysis (PD patients) whose age range was 2–14 years, and 25 of them were on continuous ambulatory PD while 4 were treated by continuous cycling PD; 36 nondialyzed (age range 2–16 years) CRF patients (ND patients) were also included. There was a statistically significant difference in age between the PD and HD groups (p = 0.013). All HD patients were treated by bicarbonate dialysis 3 times weekly with 0.4–0.7 m 2 substituted cellulosic membranes. PD was carried out 4–6 times daily in continuous ambulatory PD patients and for 8–10 h/night in continuous cycling PD patients with 1.36% peritoneal dialysis solutions (Dianeal 1.36%, Baxter-Eczacibasi Healthcare, Istanbul, Turkey). There was no medication by mannitol in any groups. Samples of blood were obtained before and

Association of eNOS gene intron 4 a/b VNTR polymorphisms in children with nephrotic syndrome.

To investigate the association of endothelial nitric oxide synthase gene intron 4 (eNOS4) polymorphisms with nephrotic syndrome, the eNOS4 genotypes were assessed in 161 children with nephrotic syndrome in comparison with 78 healthy subjects. We classified the children with nephritic syndrome into 2 groups: as steroid-sensitive nephrotic syndrome (SSNS) (n=125) and steroid-resistant nephrotic syndrome (SRNS) (n=36). The eNOS4 polymorphisms were analyzed by polymerase chain reaction. The frequencies of eNOS4 aa, ab and bb genotypes were 3%, 31%, and 66% in all the nephrotic syndrome groups, and 1%, 23%, and 76% in the control group (x(2)=2.87, p>0.05). In addition, the frequencies of eNOS4 aa, ab and bb genotypes were 2%, 33%, and 65% in SSNS group, and 5%, 28%, and 67% in the SRNS group (x(2)=1.13, p=0.567). The present study is the first to investigate eNOS4 gene polymorphisms in children with SSNS and SRNS. Our data show that the eNOS4 gene polymorphisms were not associated with the development, frequent relapse and response to steroid in nephritic syndrome.