Naci Çine

Association of MDR1 (C3435T) Polymorphism and Resistance to Carbamazepine in Epileptic Patients from Turkey

Background and Aims: We investigated the prevalence of this multidrug resistance 1 gene (MDR1) polymorphism in drug-responsive versus drug-resistant epilepsy patients treated with carbamazepine (CBZ), which is a substrate of this protein. Methods: We genotyped the C3435T variant of MDR1 in 97 patients treated with CBZ monotherapy who had been on stable doses for more than 1 month. Our control group included 174 healthy individuals. Plasma CBZ concentrations were also measured using fluorescence polarization immunoassay. Results: We could not demonstrate any statistically significant relationship with the genotypes among drug-resistant patients (n = 44). The frequency of the homozygous mutant (TT) genotype was 15% in drug-responsive patients, 11.3% in drug-resistant patients and 25.8% in the control group. We also did not observe any significant correlation between the presence of a specific allele and CBZ plasma level/dose index. Conclusion: Our study did not support any significant association between the MDR1 (C3435T) polymorphism and resistance to CBZ in epilepsy patients from Turkey.

Role of the mutations Trp8 ⇒ Arg and Ile15 ⇒ Thr of the human luteinizing hormone β-subunit in women with polycystic ovary syndrome

OBJECTIVE To evaluate the clinical significance of LH in the form of a mutant beta-subunit in women with polycystic ovary syndrome (PCOS). DESIGN Prospective, controlled study. SETTING University hospital. PATIENT(S) Thirty healthy women and 30 women with PCOS. INTERVENTION(S) Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Nucleotide mutations within codons 8 and 15 in the LH beta-subunit gene (Trp8 => Arg and Ile15 => Thr) were analyzed with the use of polymerase chain reaction and subsequent restriction fragment length polymorphism. MAIN OUTCOME MEASURE(S) Serum levels of gonadotropins, androgens, E2, and prolactin were determined, and the results of restriction fragment length polymorphism were analyzed. RESULT(S) Five women in the control group and one woman in the PCOS group were found to be affected by the LHbeta gene mutations. No difference was observed in serum androgen and E2 levels between the affected women and 25 healthy women who were homozygous for the wild-type LH. However, women whose serum LH levels were < or = 5.1 mIU/mL had a higher risk of having mutant LH. CONCLUSION(S) The frequency of LH mutations in women with PCOS is similar to that in healthy women. The presence of the variant does not cause any significant change in serum levels of androgens and E2.

Endothelial dysfunction in patients with asthma: the role of polymorphisms of ACE and endothelial NOS genes.

Objectives. Polymorphisms of the angiotensin converting enzyme (ACE) and endothelial nitric oxide (eNOS) genes have been implicated in asthma pathogenesis. Angiotensin II and NO have important roles in maintaining vascular tone. In this study, the relationship between endothelial dysfunction and ACE and eNOS gene polymorphisms was investigated in patients with asthma. Methods. This cross‐sectional, controlled study was conducted at the Yedikule Chest Disease Hospital and Cardiology Center in a University Hospital. Forty‐nine patients with asthma (18 male, 31 female; mean age: 33 ± 12 years) and 49 age‐ and sex‐matched healthy controls (20 male, 29 female; mean age: 30 ± 8 years) were included. Pulmonary function tests and flow‐mediated dilatation of the brachial artery [endothelium dependent dilatation (EDD)] were examined by high‐resolution ultrasonography. The ACE and eNOS genotypes were determined by PCR. Results. Asthma patients showed lower EDD (12 ± 6% vs. 22 ± 6%, p < 0.001) as compared to controls. The EDD was correlated with both predicted value of FEV1 (r = 0.31, p = 0.04) and predicted value of FVC (r = 0.37, p = 0.013). Conversely, EDD values in patients with moderate asthma were significantly lower than those in patients with mild asthma (10.1 ± 5.2% vs. 14.1 ± 5.7%, p = 0.017). However, the ACE and eNOS genotype distribution was not significantly different between controls and asthma groups. Furthermore, EDD was not associated with both gene polymorphism of ACE and eNOS. Conclusion. Patients with asthma have decreased vasodilatatory response to shear stress (EDD). Decreased EDD is correlated with the severity of asthma, but not with the distribution of ACE and eNOS genotypes.

Association of a polymorphism of the ecNOS gene with myocardial infarction in a subgroup of Turkish MI patients.

In this study we examined a possible association between a 27 base pair (bp)‐repeat polymorphism in intron 4 of the ecNOS gene and myocardial infarction (MI) in a subgroup of the Turkish population. We compared MI and control groups for the frequencies of the ecNOS alleles and their genotypes. The frequency of the ecNOS 4a/a and 4a/b genotypes was found to be significantly higher in the MI group than in the control group. Interestingly, the frequency of the ecNOS 4a/b polymorphism was found to be significantly higher in the selected MI group (patients with no known secondary risk factors) than in the control and non‐selected MI group. We found that the patients with MI had the frequency of the a/a genotype 4.3%, of the a/b genotype 26.6% and the b/b genotype 69.1%. The controls, however, showed only 0.6% for a/a, 18.0% for a/b and 81.4% for the b/b genotype (P < 0.001; χ2 = 13.626). In this study, we show that myocardial infarction is associated with one subtype of ecNOS gene polymorphism.

The effect of angiotensin converting enzyme gene polymorphism on chronic allograft dysfunction in living donor renal transplant recipients.

Background. Chronic allograft dysfunction (CAD), the major cause of the failure of kidney allografts, may be caused by immunological and non‐immunological haemodynamic factors. Renin–angiotensin system has been implicated in the development of intraglomerular hypertension and has a central role on progression in chronic renal disease. Polymorphism in 16th intron of the ACE gene has been reported to predict the circulating angiotensin II levels. The aim of this study was to investigate the effect of the both recipient and donor angiotensin converting enzyme (ACE) genotype on the development of CAD in renal allograft recipients.

No Association between Deletion-Type Angiotensin-Converting Enzyme Gene Polymorphism and Left-Ventricular Hypertrophy in Hemodialysis Patients

Left-ventricular hypertrophy (LVH), a bad prognostic sign, is a common finding in hemodialysis patients. The aim of the study was to analyze factors, including angiotensin-converting enzyme (ACE) genotype that may have an effect on the development of LVH in hemodialysis patients. Seventy-nine hemodialysis patients (42 males, 37 females, mean age 37.7 ± 13.1 years) and 82 age- and sex-matched normotensive healthy controls (40 males, 42 females, mean age 35.6 ± 5.7 years) were included. Left-ventricular mass index (LVMI) was higher in the hemodialysis group compared to controls (170.1 ± 69.3 versus 84.9 ± 15.7 g/m2, p < 0.001). Fourty-three hypertensive patients in the hemodialysis group had an increased LVMI compared to 36 normotensive hemodialysis patients (194.2 ± 75.5 versus 141.2 ± 48.0 g/m2, p < 0.001). On univariate analysis, LVMI was found to be correlated with blood pressure (r = 0.38, p < 0.001), time spent on dialysis (r = 0.22, p = 0.02) and hemoglobin levels (r = –0.21, p = 0.03). No correlation was found between LVMI and age (r = 0.09, p = 0.22), predialytic creatinine (r = 0.09, p = 0.21) and albumin (r = –0.10, p = 0.18). On multivariate analysis for the predictors of LVMI, blood pressure, time spent on dialysis and hemoglobin levels were also found to be significant. LVMI in DD, ID and II genotypes were 155.0 ± 71.2, 181.6 ± 60.6, and 163.6 ± 83.4 g/m2, respectively (p > 0.05). No association between LVMI and DD genotype was found. ACE genotype distribution was similar in hemodialysis patients and healthy controls. It was concluded that LVH in hemodialysis patients was mainly related to hypertension, anemia and time spent on dialysis and the DD genotype had no effect on LVMI in hemodialysis patients.

Evaluation of Glutathione S-Transferase P1 Polymorphisms (Ile105Val and Ala114Val) in Patients with Small Cell Lung Cancer

AIMS Glutathione S-transferase P1 (GSTP1) plays an important role in cellular protection against oxidative stress and toxic chemicals. Polymorphisms within GSTP1 are associated with alterations in enzyme activity, which may lead to development of lung disease and cancer. In this study, we aimed to investigate the GSTP1 Ile105Val and Ala114Val polymorphisms in patients with small cell lung cancer (SCLC). PATIENTS/METHODS GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala114Val polymorphism in exon 6 were determined by using polymerase chain reaction-restriction fragment length polymorphism techniques in 89 patients with SCLC and 108 control patients with chronic obstructive pulmonary disease (COPD). Genotype frequencies and cigarette smoking intensities were compared among SCLC and COPD patients. RESULTS There were significantly less SCLC patients with variant exon 6 genotypes than COPD patients (7.9% vs. 20.4%, p=0.007), while the number of patients with variant exon 5 genotypes were comparable among groups. SCLC and COPD patients with variant exon 6 genotype showed trends toward exhibiting reduced cigarette consumption. CONCLUSIONS The variant GSTP1 exon 6 genotype might be conferring protection against SCLC development. Whether this effect is associated with exposure to cigarette smoking needs to be clarified.

Autosomal Recessive Idiopathic Epilepsy in an Inbred Family from Turkey : Identification of a Putative Locus on Chromosome 9q32-33

Summary:  Purpose: The study describes the clinical features of an inbred family from Turkey with three members affected by seizures and tests possible autosomal recessive (AR) inheritance by means of linkage analysis.

Leptin receptor variant in women with polycystic ovary syndrome.

The polycystic ovary syndrome was diagnosed according to the following criteria: [1] bilateral polycystic ovaries on ultrasonography; [2] oligomenorrhea or amenorrhea, hirsutism, obesity, or chronic anovulation, or any combination of these conditions; [3] hyperandrogenemia (elevated serum levels of testosterone, free testosterone, or androstenedione); [4] elevated serum LH levels; and [5] exclusion of late-onset congenital adrenal hyperplasia and ovarian and adrenal tumors. All women with PCOS were euthyroid and had normal serum prolactin levels.

Expression analysis and clinical correlation of aquaporin 1 and 4 genes in human hippocampal sclerosis

Mesial temporal sclerosis (MTS) is the most frequent cause of drug resistant symptomatic partial epilepsy. The mechanism and genetic background of this unique pathology are not well understood. Aquaporins (AQP) are regulators of water homeostasis in the brain and are expressed in the human hippocampus. We explored the role of AQP genes in the pathogenetic mechanisms of MTS through an evaluation of gene expression in surgically removed human brain tissue. We analyzed AQP1 and 4 mRNA levels by quantitative real-time polymerase chain reaction and normalized to ABL and cyclophilin genes, followed by immunohistochemistry for AQP4. Relative expressions were calculated according to the delta Ct method and the results were compared using the Mann-Whitney U test. Brain specimens of 23 patients with epilepsy who had undergone surgery for MTS and seven control autopsy specimens were investigated. Clinical findings were concordant with previous studies and 61% of the patients were seizure-free in the postoperative period. AQP1 and 4 gene expression levels did not differ between MTS patients and control groups. Immunofluorescence analysis of AQP4 supported the expression results, showing no difference. Previous studies have reported contradictory results about the expression levels of AQP in MTS. To our knowledge, only one study has suggested upregulation whereas the other indicated downregulation of perivascular AQP4. Our study did not support these findings and may rule out the involvement of AQP in human MTS.