Emriye Ferda Perçin

Development of a new real-time PCR screening kit for HbS and common beta-thalassemia mutations observed in Turkey

BACKGROUND/AIM IVSI-110 (G>A), IVSI-6 (T>C), IVSII-1 (G>A), IVSII-745 (C>G), IVSI-1 (G>A), and HbS are mutations covering 76% of all the β-globin mutations in the Turkish population. In this study, our aim is to develop a reliable, fast, real-time kit for these mutations using the TaqMan probe method. MATERIALS AND METHODS This study included 100 individuals with beta-thalassemia or sickle cell anemia who had unknown mutations, and 21 controls with known mutations. RESULTS We designed a kit containing the IVSI-110 (G>A), IVSI-6 (T>C), IVSII-1 (G>A), IVSII-745 (C>G), IVSI-1 (G>A), and HbS mutations by using the real-time PCR method. One hundred patients were studied with our developed TaqMan real-time PCR kit. Of these patients, 73 (73%) were identified with the beta gene mutation. Among those 73 patients, 16 were homozygous, 54 were heterozygous, and 3 were compound heterozygous. CONCLUSION This reliable kit provided rapid diagnosis including 76% of the β-thalassemia mutations in Turkey.

Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population

Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.

T102C and 1438 G/A Polymorphisms of the Serotonin 2A Receptor Gene in Etiology and Course of ADHD

Abstract The aim of this study was to investigate the -1438A>G and T102C polymorphisms of serotonin 2A (5-HT2A) receptor gene frequencies in patients with ADHD compared with a healthy control group, and to determine the effects of these polymorphisms on the course and outcome of ADHD. Fifty adolescents and young adults diagnosed with ADHD in childhood (between 1994 and 2001) were included in this study. The patients were followed in the Child and Adolescent Psychiatry Department of Gazi University Medical Faculty for 7–14 years, and they completed this follow-up period. The control group consisted of 50 adolescents and young adults who were healthy both physically and mentally. In adolescence and adulthood, a diagnosis was reached after a semistructured interview based on the DSM-IV criteria. A genetic evaluation was carried out using the Polymerase Chain Reaction method. 50 adolescents and young adults (39 males, 11 females; age range 16-25 years) who were diagnosed with ADHD during childhood (age range at the time of diagnosis 6–10 years) and 50 healthy adolescents and young adults (33 males, 17 females; age range 16-25 years) were evaluated. In adolescence and adulthood, the diagnosis of ADHD remained in 44 (88%) of the cases, whereas six (12%) were in remission after the 7–14-year follow-up.* No significant difference in the frequency of CC, CT and TT genotypes of T102C polymorphism (χ2=1.629, p=0.44) and AA, AG and GG genotypes of -1438A>G polymorphism (χ2= 0.065, p=0.96) was found between the ADHD and control groups. No significant difference was found between ADHD patients with CC, CT, or TT genotypes in terms of the outcome of the illness (χ2=0.114, p=0.94). Similarly, there was no difference between ADHD patients with AA, AG, and GG genotypes in terms of the outcome (χ2=0.530, p=0.76). No significant association between -1438A>G and T102C polymorphisms of the 5-HT2A receptor gene and ADHD was found in the present study. No significant effect of these two polymorphisms on the outcome of ADHD in adolescence was detected. The results of this study do not support a role for the serotonergic system in the development and course of ADHD.