Mutlu Karkucak

Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism.

Objective  Nonsyndromic autosomal recessively inherited nongoitrous congenital hypothyroidism (CHNG) can be caused by mutations in TSHR, PAX8, TSHB and NKX2‐5. We aimed to investigate mutational frequencies of these genes and genotype/phenotype correlations in consanguineous families with CHNG.

GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer

OBJECTIVE This work investigates the role of glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and glutathione S-transferase P1 (GSTP1) enzymes and polymorphisms, which are found in phase II detoxification reactions in the development of cervical cancer. METHODS This study was conducted with 46 patients diagnosed with cervical cancer and 52 people with no cancer history. Multiplex PCR methods were used to evaluate the GSTM1 and GSTT1 gene polymorphism. However, the GSTP1 (Ile105Val) gene polymorphism was studied using a PCR-RFLP method. The patient and control groups were compared using a chi-square test with p<0.05. RESULTS In the patient group, statistical significance was determined for gravidity (p=0.03), parity (p=0.01), and the number of living children (p=0.01) compared to the control group. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphisms was evaluated. We observed that GSTM1 and GSTT1 null genotype frequencies were 54.3% and 32.6% respectively, while GSTP1 (Ile/Val), (Ile/Ile), (Val/Val) genotype frequencies were 52%, 44%, and 4%, respectively, in the cervical cancer patients. No statistical variation was determined between the control and patient groups in terms of GSTM1, GSTT1, and GSTP1 polymorphisms (p>0.05). CONCLUSION Our results demonstrate that GSTT1, GSTM1, and GSTP1 polymorphisms are not associated with cervical cancer in Turkish patients.

XRCC1 Gene Polymorphisms and Risk of Lung Cancer in Turkish Patients

Abstract Polymorphisms in the X-ray repair cross complementing 1 (XRCC1) gene have been found to be associated with susceptibility to various types of cancers. We investigated the association between the XRCC1 gene Arg399Gln polymorphism and the susceptibility to lung cancer in Turkish patients. To determine the association of this polymorphism with the risk of lung cancer in Turkish patients, a hospital-based case-control study was designed, involving 67 patients with lung cancer and 60 control subjects with no cancer history who were matched for age and gender. XRCC1 genotypes (Arg/Arg, Arg/Gln, and Gln/Gln) were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis on genomic DNA. No statistically significant relationship was determined between the lung cancer and control groups (p>0.05). Among the patients, 61% were Arg/Arg, 28% were Arg/Gln, and 11% were Gln/Gln. Among the controls, 50% were Arg/Arg, 38% were Arg/Gln, and 12% were Gln/Gln. There was no difference in the distribution of XRCC1 genotypes or the frequencies of the Arg (75% versus 69%) and Gln (25% versus 31%) alleles between the lung cancer patients and controls. Our results suggest that the XRCC1 gene Arg399Gln polymorphism is not associated with an increased risk for the development of lung cancer in Turkish patients.

Investigation of GSTP1 (Ile105V al) Gene Polymorphism in Chronic Myeloid Leukaemia Patients

Abstract The factors leading to the development of Chronic Myeloid Leukemia (CML) are not fully known. Associations between polymorphisms for genes encoding Glutathione S-transferase (GST) enzymes involved in Phase II detoxification reactions and susceptibility to some cancers have been shown in several studies. The aim of the present study was to investigate the influence of the GSTP1 (IIe105Val) gene polymorphism on human susceptibility to CML. Seventy-one CML patients and 67 control subjects with no cancer history were enrolled in our study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the GSTP1 (lle105Val) gene polymorphism. Genotypes were determined according to the bands that formed in agarose gels via gel electrophoresis. Leukocytes in the CML patient group were significantly different from those in the control group (p=0.0001). The frequency of the GSTP1 Val allele was found to be 22% in CML patients and 31% in controls. However, no statistical variation was found to exist between controls and patients in terms of the GSTP1 Val allele frequency (p=0.199). The relationship between the GSTP1 (IIe105Val) gene polymorphism and CML is not fully understood. Our results provide no evidence of a relationship between the GSTP1 (IIe105Val) gene polymorphism and susceptibility to CML in Turkish patients. However, these findings should be confirmed in studies with larger sample sizes.

AML1 amplification and 17q25 deletion in a case of childhood acute lymphoblastic leukemia

We report a case of childhood acute lymphoblastic leukemia (ALL) with both acute myeloid leukemia 1 (AML1) amplification and 17q25 deletion. AML1 gene is located on 21q22 and encodes a transcription factor. AML1 amplification is a common finding in childhood ALL, and itis observed as an increase in gene copy number by the FISH analysis. The mechanism of AML1 amplification is not associated with AML1 gene mutations. The 17q25 is a gene‐rich chromosomal location and distinct abnormalities of this region have been observed in previous cases of different kinds of leukemia. Deletion of the 17q25 region has been reported in two leukemia patients. Septin 9 (SEPT9) and survivin genes are located on 17q25. High expression of these genes and AML1 amplification are regarded as markers in tumorigenesis and disease progression; however, more data are needed for accurate prognostic evaluation. J. Clin. Lab. Anal. 23:368–371, 2009.

Does MBL2 codon 54 polymorphism play a role in the pathogenesis of psoriasis

Background  Psoriasis is a T cell‐mediated immune disease in which various cytokines, primarily tumor necrosis factor‐α (TNF‐α), are complexly involved. Mannose‐binding lectin (MBL) gene polymorphisms decrease MBL serum levels, thereby increasing the synthesis of proinflammatory cytokines such as TNF‐α.

Effect of cycline D1 (CCND1) gene polymorphism on tumor formation and behavior in patients with prolactinoma

The objective of this study was to investigate the effect of G870A gene polymorphism of CCND1 on the formation and behavioral features of prolactinomas. One hundred and thirteen patients with prolactinoma and 108 age and gender matched control were included in the study. The patients were divided into two groups as noninvasive and invasive tumors. CCND1 G870A gene polymorphism was compared in patients/control and invasive/noninvasive groups. A and G allele frequencies were found as 41.7% and 58.3% in the controls, and 61.1% and 38.9% in the patients (p<0.01). Rates of G/G, G/A and A/A genotypes were found as 11.8%, 55.9% and 32.4% in the noninvasive group, and 15.6%, 44.4% and 40.0% in the invasive group, respectively. Differences between patient and control groups were significant but were not between invasive and noninvasive groups in terms of the allele frequencies and genotype distribution. Mean tumor size and serum levels of prolactin at the time of diagnosis and change in these values after the treatment were not found statistically significant in genotype subgroups. CCND1 G870A gene polymorphism may be an important factor in the early stages of the tumor formation. However, it did not affect the features of the tumor.

Sudden blastic crisis and additional chromosomal abnormalities during chronic myeloid leukemia in the imatinib era

Imatinib has shown significant clinical and cytogenetic success in the treatment of chronic myeloid leukemia. Although resistance has been observed in a proportion of patients, sudden blastic crisis is a rare event during imatinib therapy. We describe a 24-year-old male patient with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who developed sudden blastic crisis in the 24th month of imatinib therapy, with loss of complete cytogenetic response. At this time, the patient had splenomegaly, severe anemia, thrombocytopenia, and leukocytosis. Bone marrow aspirate revealed the presence of massive blastic infiltration with myeloid morphology. Flow cytometric analysis of the bone marrow cells showed positivity for CD45, CD34, CD13, CD33, CD19, CD41, CD61, and glycophorin-A. Trephine biopsy specimens showed 100% cellular marrow with diffuse infiltrate by blasts. A reticulin stain of the bone marrow biopsy section demonstrated severe diffuse fibrosis. Cytogenetic analysis by fluorescence in situ hybridization (FISH) revealed that 92% of the cells were positive for the BCR/ABL fusion signal and had increased copy numbers for chromosomes 8, 13, 19, and 21. The patient’s prognosis was unfavorable. In conclusion, chronic myeloid leukemia remains complex and includes unanswered questions. The presented case with a rare event during imatinib therapy highlights the need for the continued monitoring of residual disease and the development of strategies to eliminate residual leukemia cells in patients showing a complete cytogenetic response.

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism in Patients with Pulmonary Thromboembolism

Abstract The aim of the present study is to investigate the relationship between angiotensin-converting enzyme (ACE) gene polymorphism and pulmonary embolism by comparing the frequency of ACE gene polymorphism between cases diagnosed with pulmonary embolism with that of the control group. The study included 73 patients and 73 healthy subjects as the control group. Isolated DNAs were genotyped using the polymerase chain reaction (PCR) method for the identification of the ACE insertion/deletion (I/D) polymorphism. The genotypes were determined according to the bands observed in the agarose gel electrophoresis. The frequency of ID genotype was 39.7 percent, the frequency of insertion/insertion (II) genotype was 17.8 percent, and the frequency of the deletion/deletion (DD) genotype was 42.5 percent in the patient group. In the control group, the frequency of the II genotype was 21.9 percent, the frequency of the ID genotype was 38.4 percent, and the frequency of the DD genotype was 39.7 percent. There were no statistically significant differences between the patient group and the control group in terms of the frequencies of II, ID, and DD genotypes (p > 0.05). The findings of the present study showed no association between ACE gene polymorphism and the risk of developing the pulmonary embolism. Due to the limited number of patients however, these results must be confirmed by further studies incorporating larger series of patients.

Investigation of Monnose-Binding Lectin gene Polymorphism in Patients with Erythema Multiforme, Stevens-Johnson Syndrome and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Overlap Syndrome

OBJECTIVE Monnose-Binding lectin (MBL) appears to play an important role in the immune system. The genetic polymorphisms in the MBL2 gene can result in a reduction of serum levels, leading to a predisposition to recurrent infection. The aim of this study is to investigate the influence of a polymorphism in codon 54 of the MBL2 gene on the susceptibility to Erythema Multiforme, Stevens-Johnson Syndrome and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Overlap Syndrome (EM, SJS and SJS/TEN overlap syndrome). MATERIAL AND METHODS Our study included 64 patients who were clinically and/or histopathologically diagnosed with EM, SJS, and SJS/TEN overlap syndrome and 66 healthy control subjects who were genotyped for the MBL2 gene codon 54 polymorphism using the PCR-RFLP method. For all statistical analyses, the level of significance was set at p<0.05. RESULTS The prevalence of the B allele was 18% in the EM, SJS and SJS/TEN patient groups and 13% in the control group. No significant differences in allele frequencies of any polymorphism were observed between the patient and control groups, although the B allele was more frequent in the patient groups (p=0.328). CONCLUSION Our results provide no evidence of a relationship between MBL2 gene codon 54 polymorphism and the susceptibility to EM, SJS and SJS/ TEN overlap syndrome. However, these findings should be confirmed in studies with a larger sample size.