Salih Kozan

Mitochondrial complex I and III gene mRNA levels in schizophrenia, and their relationship with clinical features.

BackgroundThe etiology of schizophrenia is not precisely known; however, mitochondrial function and cerebral energy metabolism abnormalities were determined to be possible factors associated with the etiology of schizophrenia. Impaired mitochondrial function negatively affects neuronal plasticity, and can cause cognitive deficits and behavioral abnormalities observed during the clinical course of schizophrenia. The present study aimed to investigate the relationship between the clinical features of schizophrenia, and mitochondrial complex activation, based on measurement of mRNA levels in the NDUFV1, NDUFV2, NDUFS1, and UQCR10 genes involved in the peripheral mitochondrial complex.MethodsThe study included 138 schizophrenia patients and 42 healthy controls. The schizophrenia group was divided into a chronic schizophrenia subgroup (n = 84) and a first-episode schizophrenia subgroup (n = 54). The symptoms profile and severity of disorder were evaluated using the Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Brief Psychiatric Rating Scale (BPRS).ResultsThe level of mRNA expression of NDUFV1, NDUFV2, and NDUFS1 was significantly higher in the schizophrenia group than in the control group. The mRNA level of NDUFV2 was positively correlated with BPRS and SAPS scores in the first-episode schizophrenia subgroup.ConclusionThe findings showed that there was a positive correlation between gene mRNA levels and psychotic symptomatology, especially positive symptoms. Our results suggest that mRNA levels of the NDUFV1, NUDFV2, and NDUFS1 genes of complex I of the mitochondrial electron transport chain might become a possible peripheral marker for the diagnosis of schizophrenia.

Mitochondrial complex I and III mRNA levels in bipolar disorder

BACKGROUND Studies that have focused on the mitochondrial electron transport chain indicate that bipolar disorder (BD) is associated with pathology in mitochondrial function. These pathological processes occur in the brain circuits that regulate affective functions, emotions, and motor behaviors. The present study aimed to determine the relationship between mitochondrial complex dysfunction and BD. METHODS The BD group included 32 male patients diagnosed with first-episode manic BD. The control group included 35 sociodemographically matched healthy males. Messenger ribonucleic acid (mRNA) was isolated from peripheral blood samples obtained from the patients and control group, and the mRNA levels of the NDUFV1, NDUFV2, and NDUFS1 genes of mitochondrial complex I and the UQCR10 gene of mitochondrial complex III were investigated. RESULTS Significant differences were identified in complex I gene mRNA levels between the BD group (n = 32) and the control group (n = 35) for the following genes: NDUFV1 (P = 0.01), NDUFV2 (P < 0.01), and NDUFS1 (P = 0.02). The UQCR10 gene (complex III) mRNA level did not differ between the groups (P = 0.1). The mRNA levels of the four genes studied were lower at the 3-month follow-up; however, these differences were not significant (P > 0.05). LIMITATIONS All of the BD patients were in manic episodes; thus, we were unable to separately compare these levels with those during depressive and euthymic episodes. CONCLUSIONS The mRNA levels of all of the genes representing the subunits of mitochondrial complex I (NDUFV1, NDUFV2, and NDUFS1) were significantly higher in the present studys BD patients during manic episodes than in the controls. With the data obtained from further research, biomarkers that could be used for the diagnosis and follow-up of neuropsychiatric disorders may be discovered.

The association of nonalcoholic fatty liver disease with genetic polymorphisms: a multicenter study

Introduction Growing evidence suggests that multiple factors, such as insulin resistance, nutritional factors, gut microbiota, and hormones released from the adipose tissue, act together on genetically predisposed individuals. We aimed to investigate whether various single-nucleotide polymorphisms (SNPs) play a role in the development of nonalcoholic fatty liver disease (NAFLD) and severity of liver damage in the Anatolian population. Methods Two hundred and sixteen patients with biopsy-proven NAFLD and 150 control participants, aged 18–70 years, were consecutively enrolled in this multicenter study. Blood samples were genotyped for the PNPLA3 (rs738409), IL28B (rs12979860, rs12980275, rs8099917), PPAR-&agr; 227 ALA, PPAR-&ggr; pro 12 ALA, SOD2 C47T, and LOX-1 IVS4–14 polymorphisms using the custom-made LightSNiP assays on a LightCycler 480 II instrument. Results Genotypic distributions of PNPLA3 rs738409 SNPs were different between NAFLD and control participants, but not for other SNPs. The PNPLA3 rs738409 GG polymorphism was associated with a 27-fold increased risk of development of NAFLD (odds ratio=27.8, 95% confidence interval: 3.5–218.4; P=0.002). Patients with the PNPLA3 GG genotype had higher nonalcoholic fatty liver disease activity score levels compared with patients with the PNPLA3 CC genotype (P<0.005). NAFLD patients without fibrosis had a higher frequency of IL28B rs12979860 TT and rs12980275 GG genotypes compared with NAFLD patients with fibrosis (P<0.005). Conclusion The present study proposes that polymorphisms in the PNPLA3 gene have highly predictive value in the development of NAFLD and are independently associated with the severity of liver histology in patients with NAFLD. The results of this study suggest that IL28B rs12979860 TT or rs12980275 GG may play an important protective role against the development of advanced fibrosis and even cirrhosis.

UNILATERAL TUBAL ECTOPIC TWIN PREGNANCY

Ectopic pregnancies develop when conception products implant somewhere other than in the endometrial cavity. If these pregnancies are not diagnosed and treated early, they can affect fertility and threaten the lives of otherwise healthy women. Twin pregnancies develop in approximately 1 in every 80 spontaneous pregnancies, and heterotopic pregnancies occur in about 1 in every 7,000 spontaneous pregnancies [1]. The probability of developing a unilateral tubal twin pregnancy has been calculated as 1 in every 125,000 spontaneous pregnancies. Most unilateral tubal twin gestations are reported to be monochorionic and monoamniotic [2]. A 24-year-old patient with a 5-week history of amenorrhea was admitted to our clinic with a complaint of left pelvic pain and vaginal bleeding which had lasted for 3 days. At admission, the patient was generally well and was conscious, cooperative and well-oriented. Her medical history revealed that she had been married for 3 months and was nulligravid, but used no contraception and had been planning on having children. The patient’s blood pressure was 120/80 mmHg, her pulse was 84 beats/minute, and her temperature was 37°C. Pelvic examination revealed extrauterine vaginal bleeding, closed cervical os, pain on cervical movement during manual examination, and left adnexal fullness and sensitivity. Abdominal examination revealed only left lower quadrant sensitivity. The left ovary appeared normal, but transvaginal ultrasound demonstrated an approximately 4 cm-sized left juxtauterine mass and free fluid in the left paraovarian area. Laboratory findings included a β-human chorionic

Methylation of SOCS3 in Myeloproliferative Neoplasms and Secondary Erythrocytosis/Thrombocythemia

Objective: Myeloproliferative neoplasms (MPNs) like essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are acquired clonal hematopoietic stem cell disorders and originate from a multipotent hematopoietic stem cell. The SOCS1 and SOCS3 genes are negative regulators of the JAK/STAT signal pathway. In this study we investigate the promoter methylation of these genes in the pathogenesis of MPNs and secondary erythrocytosis/thrombocythemia. Materials and Methods: Promoter methylation of SOCS1 and SOCS3 genes was analyzed with methylation-specific PCR. PCR products were analyzed by agarose gel electrophoresis. Results: No disease-specific CpG island methylation of SOCS1 was observed. Hypermethylation of the SOCS3 promoter was identified in 5 out of 19 (26.3%) PV cases, 2 out of 21 (9.5%) ET cases, 1 out of 5 (20%) PMF cases, and 9 out of 42 (21.4%) cases of secondary erythrocytosis/thrombocythemia. Conclusion: The results revealed that promoter methylation of the SOCS3 gene suggests a possible role for SOCS3 methylation in the pathogenesis of MPNs and secondary erythrocytosis/thrombocythemia. Conflict of interest:None declared.

Rare chromosomal complement of trisomy 21 in a boy conceived only by IVF.

In the article ‘Rare chromosomal complement of trisomy 21 in a boy conceived by IVF and cryopreservation’ presented in Reproductive BioMedicine Online (Quiroga et al., 2009) a case of mosaic Down syndrome with an unusual karyotype was reported. The chromosomal complement consisted of two different cell lines, one predominantly trisomic with a derivative chromosome due to a Robertsonian translocation (21;21) and another carrying a ring chromosome 21. The assisted reproductive techniques and cryopreservation were held responsible in this rare type of mosaic Down syndrome case. This letter presents a similar case with three different cell lines including predominantly a ring 21 chromosome, a Robertsonian translocation (21;21) and a monosomy 21 (Figure 1). The karyotype was 46,XY r(21) [87], 45,XY, 21 [21], 46,XY, t(21;21)(q10;q10) [6] (Figure 1). This one-month old case was born to a non-consanguineous family as the first child. His mother was 29 years old and his father was

Is Turkey a prothrombin gene mutation region similar to the Mediterranean countries

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide (1). Acute MI generally develops following a critical narrowing of the coronary artery or a narrowing or complete occlusion of the coronary vessel by an acute plaque rupture (2). MI in young adults may be categorized into two groups as normal coronary artery anatomy and coronary artery disease (CAD) accompanied by various etiologies; moreover, conditions associated with hypercoagulopathy play a significant role in the pathophysiology of both groups (3). We examined 68 patients (aged <45 years) with ACS and 69 healthy controls for hypercoagulable states in our institution between January 2008 and June 2010. We found a statistically significant difference between the groups for factor V Leiden (FVL), whereas there was no statistically significant difference for prothrombin gene mutation (P G20210A). The two most common reasons of familial thrombophilia are P G20210A and FVL. P G20210A is frequently observed in Southern European countries and most notably in countries that have coast to the Mediterranean (4). Despite conflicting results, some studies have demonstrated that the combination of known risk factors and P G20210A is a risk factor for the development of arterial thrombus and ACS (5). In our study, there was no statistically significant difference between the patient and control groups (2.9% vs. 1.4%, p=0.551). P G20210A was found to be heterozygotic in three (2.2%) among a total of 137 cases. However, in the study by Akar et al. (6), P G20210A prevalence rate in Turkey was reported to be 6.2%, which is similar to the rate in Mediterranean countries; however, this finding is contradictory to our study findings. Despite being a Mediterranean country, Turkey is located right in the middle of three continents and has a distinctive geography. Therefore, FVL mutation prevalence rather than P G20210A may be more frequent, particularly in the Central Anatolian, Eastern Anatolian, and Black Sea Regions, which is similar to that observed in the Northern European countries. Data regarding the association of FVL mutation with the development of CAD and ACS are conflicting. However, large studies investigating young patients with ACS have reported that FVL mutation was found to be statistically significant (7). Similarly, we found in our study that FVL mutation was statistically significant in the patient group compared with that in the control group (22.1% vs. 5.8%, p=0.006). In conclusion, patients with ACS carrying FVL mutation might have a role in the pathophysiology of developing ACS. Furthermore, Turkey appears as a FVL mutation region rather than a P G20210A mutation region, which is similar to the Northern European countries, thereby opposing the known current literature. However, further prospective controlled studies in larger patient populations with careful analysis of other risk factors and mutations are required to understand the pathophysiological process of ACS.

Low Zip 4 gene expression levels in RPMI - 8226 and ARH - 77 cell lines support the possible role of zip 4 transporter protein in plasma cell tumorogenesis

Abstract Aim. Multiple myeloma and plasma cell leukemia are cancers of plasma cells. Multiple myeloma rarely transforms to plasma cell leukemia during the progression period. Zinc as a chemical element modulates proliferation and differentiation of cells by affecting several growth factors. Zip 4 modifies zinc metabolism in a cell as a transporter protein. While high Zip 4 gene expression was found in pancreas and hepatocellular carcinoma, low Zip 4 gene expression was observed in prostate carcinoma. Methods. Here, Zip 4 expression levels were studied in RPMI - 8226 and ARH - 77 cell lines as examples of multiple myeloma and plasma cell leukemia, respectively. Results. We found lower Zip 4 gene expression levels in both cell lines than that of the normal control (0,000157 in RPMI - 8226, 0,000227 in ARH - 77 cell lines and 1 in normal control) The findings were statistically significant (P < 0.05). The expression levels of Z ip 4 gene in both cell lines were approximately similar. No statistical significance was found between the expression levels of Zip 4 in both cell lines (P = 0.547). Conclusion. The results of this study support the possible role of Zip 4 gene expression in plasma cell dyscrasias. The similar result of Zip 4 gene expression level in both cell lines has no role in the transformation of multiple myeloma to plasma cell leukemia. Keywords: Zip 4 gene, gene expression, multiple myeloma, plasma cell leukemia Ozet Amac. Mltipl myelom ve plazma hucreli losemi, plazma hucresinden koken alan kanserlerdir. Hastaligin ileri evresinde multipl myelom nadiren plazma hucreli losemi formuna doner. Kimyasal bir element olarak cinko farkli buyume faktorleri uzerinden memeli hucrelerinde cogalma ve farklilasmayi duzenler. Tasiyici bir protein olarak Zip 4 ise hucrede cinko metabolizmasinda aktif rol alir. Pankreas ve karaciger kanserlerinde artmis Zip 4 gen ekspresyonu bulunurken, prostat kanserinde dusuk Zip 4 gen ekspresyonu tanimlanmaktadir. Yontemler. Bu calismada, sirasi ile multipl myelom ve plazma hucreli losemilere ornek olabilecek RPMI - 8226 ve ARH - 77 hucre hatlarinda Zip 4 gen ekspresyon duzeyleri bakilmistir. Bulgular. Her iki hucre hattinda Zip 4 gen ekspresyon duzeyi normale gore daha dusuktur (RPMI - 8226 hucre hattinda 0,000157 ve ARH - 77 hucre hattinda 0,000227). Elde edilen veriler istatistiksel olarak anlamlidir (P < 0,05). Her iki hucre hattinda Zip 4 gen ekspresyon duzeyleri birbirine cok yakin olarak bulunmustur. Aralarinda istatistiksel olarak anlamli bir fark da bulunmamistir (P = 0,547). Sonuc. Sonuclar plazma hucre diskrazilerinde Zip 4 gen ekspresyonunun olasi rolunu destekler niteliktedir. Her iki hucre hattinda birbirine yakin bulunan Zip 4 gen ekpresyon duzeyinin multipl myelomanin plazma hucreli losemiye donusmesinde rolu olmadigini ortaya koymaktadir. Anahtar sozcukler: Zip 4 geni, gen ekspresyonu, multipl myelom, plazma hucreli losemi

Prostat kanserinden uzun süre sonra gelişen kompleks karyotipik anormali ile seyreden akut myeloblastik lösemi olgusu

Ozet Loseminin bir turu olan akut myeloblastik losemi (AML) myeloid seriye ait olgunlasmamis hucrelerin kemik iliginde, kanda, bazen diger dokularda asiri birikimi ile karakterize hematolojik kanserdir. Losemik hucre farklanmasinda kemik iligi ve periferik kan hucrelerinde klonal kromozomal anomaliler ortaya cikmaktadir. Bu anomaliler olgu tanisi ve prognozunu gostermesi acisindan onemlidir. Yazimizda prostat kanseri nedeni ile 12 yil once cerrahi ve hormon tedavisi alan ilk tani evresinde kompleks karyotip anomaliler tesbit edilen bir AML olgusu sunulmaktadir. Tanimlanan kompleks karyotipik anomalilerin prognoz uzerindeki etkisi tartisilmaktadir. Periferik kan ve kemik iligi incelemesinde AML tanisi konan 70 yasindaki erkek olgunun kemik iliginden yapilan sitogenetik incelemede 49, XY, -1, -2, +4, +6, +8, +8, -12, -13, der (1), +2 mar [3], 50, XY, -2, +4, +6, +8, +8, -13, +2mar [2], 50, XY, -2, +4, +6, +8, +11?, -13, +2 mar [1] saptandi. Kompleks karyotipler genelde olgularda kotu prognoz belirtecidir. AML tanisi konulan olgu her turlu destek tedavisine ragmen tanidan iki gun sonra kaybedildi. Sonuc olarak, ozellikle yasli AML’li hastalarda gerek tani, gerekse prognozun belirlenebilmesi icin genetik incelemelerin mutlaka yapilmasi gerekliligi goz onunde bulundurulmalidir. Anahtar sozcukler: Akut myeloid losemi, karyotipleme, kromozom anormallikleri, sitogenetik Abstract Acute myeloid leukemia (AML) is a type of leukemia which is characterized by the excessive accumulation of immature myeloid bone marrow precursor cells in the marrow itself, in peripheral blood and sometimes also in other tissues. During differentiation of leukemia cells, clonal chromosomal abnormalities emerge in bone marrow and in peripheral blood cells. These anomalies are important for the disease diagnosis and prognosis. Here, an AML case who underwent surgery for prostate cancer 12 years ago and received hormonal therapy is presented. Complex karyotypic abnormalities were present in the initial diagnosis phase The correlation between complex karyotypes and the prognosis in this case was discussed. Our 70 year-old patient was diagnosed as AML after peripheral blood and bone marrow analyses. His bone marrow cytogenetic analyses revealed 49, XY, -1, -2, +4, +6, +8, +8, -12, -13, der (1), +2 mar [3], 50, XY, -2, +4, +6, +8, +8, -13, +2mar [2], 50, XY, -2, +4, +6, +8, +11?, -13, +2 mar [1]. Complex karyotypes generally represents poor prognosis in AML cases. The patient died in two days after the initial diagnosis, although AML treatment was applied. As a result genetic examination should always be performed in elderly AML patients for both diagnosis and prediction of prognosis. Keywords: Acute myeloid leukemia, karyotyping, chromosome aberrations, cytogenetics

Miyelodisplastik sendromdan geçişli akut myelomonositik lösemi olgusunda monozomi 7 sitogenetik anomalisi

Myelodisplastik sendrom sitopeni ile karakterize, hematopoietik kok hucrelerin klonal bir hastaligidir. Hastalarda kemik iliginde hucre yapilmamasina bagli komplikasyonlardan, akut losemiye kadar genis bir yelpazede risk tanimlanir. Myelodisplastik sendromda ve/veya akut losemilerde prognozu belirleyen en onemli kriterlerden biri kemik iligi orneklerinin sitogenetik incelemesidir. Burada myelodisplastik sendromdan transforme akut myelomonositik losemi (Akut miyelositik losemi-M4) tanisi almis bir olgu sunulmaktadir. Diseti kanamasi, halsizlik ve kilo kaybi sikayetleri ile klinige basvuran 57 yasindaki erkek olguda, kanda yuksek lokosit sayisi dikkat cekmistir. Kemik iligi analizinde olguya akut myelomonositik losemi tanisi konmustur. Kemik iligi sitogenetik analizinde monozomi 7 ile uyumlu karyotip ornekleri tespit edilmis olup “kotu prognoz belirteci” olarak yorumlanmistir. Hastada kemoterapi surmekte olup, halen remisyon elde edilmis durumdadir