Mustafa Solak

Association of the polymorphisms of vitamin D receptor and aggrecan genes with degenerative disc disease.

The aim of this study was to investigate the association between the polymorphisms of the vitamin D receptor (VDR) and aggrecan genes and degenerative disc disease in young Turkish patients. Aggrecan and VDR proteins are the main components of bone and cartilage. In our study, the polymorphisms of the VDR and aggrecan genes were investigated in a total of 300 individuals regarding disc degeneration and herniation. An association was found in the patients having VDR gene TT, Tt, FF, and Ff genotypes with the protrusion type of disc herniation, whereas the patients having tt and ff genotypes were associated with extrusion/sequestration types of the disease. Also, an association was observed between TT and FF genotypes of the VDR gene and mild forms of disc degeneration; and tt, ff, and Ff genotypes and severe forms of the disease. There was also an association between shorter, normal, and longer alleles of the aggrecan gene and a protrusion type of disc herniation. An association was found between short alleles and multilevel and severe disc degeneration, as well as normal and long alleles and mild disc degeneration. This study revealed that the polymorphisms of the VDR and aggrecan genes are associated with disc degeneration and herniation.

Analysis of Familial Mediterranean Fever Gene Mutations in 202 Patients with Familial Mediterranean Fever

BACKGROUND Familial Mediterranean fever (FMF) is an autosomal recessive disorder, caused by mutations in MEFV gene that encodes pyrin protein. In this study, we analyzed the most common five mutations in MEFV gene of 202 patients who were diagnosed formerly as FMF according to Tel-Hashomer criteria. The results of genetical analysis, clinical symptoms, and demographical aspects of those patients were evaluated retrospectively. METHODS AND RESULTS Between the dates of February 2005 and March 2007, we analyzed five common MEFV gene mutations, which were M680I, M694V, M694I, V726A, and E148Q, in 202 patients by the PCR-ELISA method in our medical genetics laboratory. The most frequent mutation detected in our patients was M694V, and other mutations according to frequency were E148Q, M680I, V726A, and M694I. The detected mutations were homozygous in 45 of the patients (22.2%), heterozygous in 103 (51%), compound heterozygous in 52 (25.8%), and in 2 patients (1%) complex alleles were defined. The most common symptom was abdominal pain (80.4%) and other symptoms, respectively, were fever (57.8%), arthralgia (36.7%), chest pain (4.5%), and skin rash (2%). Amyloidosis was present in seven patients, and five of them had M694V mutation (homozygous), one of them had E148Q (heterozygous) mutation, and the other one had M694V/M694I mutation. CONCLUSION In our patients, we defined 21 different genotypes of MEFV gene and the most common mutation was M694V. The most common symptoms were abdominal pain and fever. We detected significant correlation between the M694V, E148Q, and V726A mutations and clinical findings.

GENETIC ANOMALIES DETECTED IN PATIENTS WITH NON-OBSTRUCTIVE AZOOSPERMIA AND OLIGOZOOSPERMIA

Genetic factors have a major importance in male infertility etiology. Numerical and structural chromosomal abnormalities seem to be frequent inoligospermia and azoospermia cases with unknown etiology. In this study, 819 patients with azoospermia (383) and oligospermia (436) who attended the infertility department between 1995–2005 were evaluated. Spermogram and basic hormone proties (FSH-testosterone) were studied two times in a one month interval from each patient, and all the cases were evaluated cytogenetically. The 47 (12%) of 383 azoospermia patients and the 20 (4%) of 436 oligospermia patients were found to have chromosomal abnormalities. The 9 (19%) of the chromosomal abnormalities found in azoospermia patients were autosomal and the 38 (80%) were gonosomal. In oligospermia cases, the 8 (40%) of the chromosomal abnormalities were autosomal and 12 (60%) were gonosomal. Cytogenetic analysis and genetic counseling would be helpful in infertile males with azoospermia and oligospermia by determining the genetic factors causing infertility and by assessing the genetic risks of the offsprigs provided by assisted reproductive techniques.

Differential expression of stem cell markers and ABCG2 in recurrent prostate cancer.

Prostate cancer (PCa) is the second most common tumor type related to mortality in males in the developed countries. Studies have demonstrated that therapeutic tools mostly ineffective to give positive outcome especially for PCa. Cancer stem cells are composed of a small cell population, which are supposed to have roles in tumorigenesis, metastasis, and tumor recurrence after chemo‐radiotherapy. The aim of this research is to investigate expressions of stem cell markers in recurrent PCa and non‐recurrent PCa tumors as well as in adjacent normal prostate tissues.

Association of estrogen receptor alpha and collagen type I alpha 1 gene polymorphisms with bone mineral density in postmenopausal women

SummaryIn this study, ERα gene PvuII and XbaI polymorphisms and COL1A1 gene Sp1 polymorphisms in postmenopausal women were compared with lumbar vertebra and femoral neck BMD values. In conclusion, it was designated that PvuII polymorphism was effective on average lumbar vertebra BMD value in postmenopausal women of our study group.IntroductionBone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a strong genetic component. Several candidate gene polymorphisms have been implicated in the regulation of this process. In this study, the relationship among BMD values of lumbar vertebra and femoral neck and ERα gene PvuII and XbaI polymorphisms and COL1A1 gene Sp1 polymorphism in 126 postmenopausal women (30 normal, 46 osteopenic, and 50 osteoporotic in terms of bone mineral density) was researched.MethodsThe ERα gene PvuII and XbaI genotypes were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) whereas the COL1A1 gene Sp1 genotype was determined by real-time PCR. BMDs at the lumbar spine (vertebrae L1–L4) and hip (femur neck) were measured by dual-energy X-ray absorptiometry.ResultsAccording to our study results, the significant difference was found in women with normal, osteopenic, and osteoporotic bone mass in terms of ERα gene PvuII polymorphism “pp” genotype frequency. The “pp” genotype frequency was significantly lower in women with normal bone mass. Average lumbar vertebra BMD value of women with “PP” genotype was significantly higher than that with “pp” genotype. On the other hand, in the evaluations on ERα gene XbaI polymorphism and COL1A1 gene Sp1 polymorphism, it was noted that there was no difference in terms of average BMD values, genotype, and allele frequencies among groups.ConclusionIn conclusion, it was designated that ERα gene PvuII polymorphism was effective on average lumbar vertebra BMD value in postmenopausal women of our study group.

Overexpression of miR-145-5p inhibits proliferation of prostate cancer cells and reduces SOX2 expression.

ABSTRACT We aimed to perform functional analysis of miR-145–5p in prostate cancer (PCa) cells and to identify targets of miR-145–5p for understanding its role in PCa pathogenesis. PC3, DU145, LNCaP PCa, and PNT1a nontumorigenic prostate cell lines were utilized for functional analysis of miR-145–5p. Its overexpression caused inhibition of proliferation through apoptosis and reduced migration in PCa cells. SOX2 expression was significantly decreased in both mRNA and protein level in miR-145–5p-overexpressed PCa cells. We proposed that miR-145–5p, being an important regulator of SOX2, carries a crucial role in PCa tumorigenesis.

Role of miR‐145 in human laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma (SCC), being an aggressive malignancy, is one of the most commonly diagnosed malignant types of head and neck SCC worldwide. Incidences of laryngeal SCC have been reported to increase recently. In this study, we aimed to explore the biological effects of miR‐145 on laryngeal cancer cells.

Radiographic evaluation and unusual bone formations in different genetic patterns in synpolydactyly

ObjectiveTo compare the radiological findings of heterozygous and homozygous subjects with synpolydactyly (SPD) and to discuss their unusual bone formations.Design and patientsFamilies with hand and foot SPD were examined. Genetic analysis was performed with blood samples and the pedigree was constructed. The affected individuals, especially those with distinctive phenotypic features, were invited to our orthopaedics clinic for further diagnostic studies. All participants underwent detailed clinical and X-ray examinations.ResultsOf the invited patients, 16 (five female and 11 male; age range 4–37 years, mean age 10.75 years) were included in our study, and hand and foot radiographs were obtained. All subjects had bilateral hand radiographs (32 hands), and 14 had bilateral foot radiographs (28 feet). Genetic analysis revealed 12 heterozygote (75%) and four (25%) homozygote phenotypes. Among patients enrolled into the study nine (three homozygotes, six heterozygotes) had SPD of both hands and feet bilaterally (tetrasynpolydactyly). Six unusual bone formations were observed in the hands and feet: delta phalanx, delta metacarpal/metatarsal, kissing delta phalanx, true double epiphysis, pseudoepiphysis and cone-shaped epiphysis. There were major differences in radiological and clinical manifestations of homozygote and heterozygote phenotypes. The homozygous SPD presented with very distinctive unusual bone formations.ConclusionThe existence and variety of unusual bones may indicate the severity of penetrance and expressivity of SPD.

Genotyping for Cx26 and Cx30 Mutations in Cases with Congenital Hearing Loss

Hearing loss is the most frequent sensory defect in human being. The 13q11-q12 region contains the GJB2 and GJB6 genes, which code connexin 26 (CX26) and connexin 30 (CX30) proteins, respectively. The 35delG, 167delT, and 235delC mutations in the Cx26 gene are the main cause for sporadic nonsyndromic hearing loss (NSHL) in many populations. The 342-kb deletion [del(GJB6-D13S1830)] of the Cx30 gene is the second most common connexin mutation after the 35delG mutation in some NSHL populations. In our study 47 hearing-impaired students were included. The Cx26 gene and the Cx30 gene were analyzed for presence of the 35delG, 167delT, and 342-kb deletion [del(GJB6-D13S1830)]. Genotyping were performed for detecting 35delG, 167delT, and del(GJB6-D13S1830) mutations using the PCR-ELISA techniques. According to the results obtained from 47 cases, the 35delG mutation was detected in 7 cases ( approximately 14.9%). Four of these mutations were determined as homozygote mutant ( approximately 8.5%), and three were determined as heterozygote mutant ( approximately 6.4%). However, 167delT and del(GJB6-D13S1830) mutations were not detected in the study group. These results support the overwhelming majority of 35delG in our study group from deafness school in our study. In conclusion, the 35delG mutation was determined as the most frequently shown mutation that leads to congenital hearing loss as in previous studies from Turkey.

Comprehensive analysis of a large-scale screen for MEFV gene mutations: do they truly provide a "heterozygote advantage" in Turkey?

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by episodes of inflammation in the absence of high-titer autoantibodies or antigen-specific T cells. The Mediterranean fever (MEFV) gene located on chromosome 16p13.3, which encodes the 781-amino-acid protein pyrin, is the causative gene for this monogenic Mendelian disease. This study presents the molecular analysis of an MEFV gene mutation screen of 5518 Turkish individuals with clinical diagnoses of FMF. Patients were genetically diagnosed using the FMF StripAssay and DNA sequencing analysis. Contrary to the results achieved by the FMF StripAssay, DNA sequencing analysis identified large-scale coding and noncoding novel sequence variants, together with a significant group (76%) of individuals who were receiving colchicine and had a single heterozygous mutation, despite the recessive inheritance of FMF. In conclusion, sequence analysis, unlike other routine laboratory techniques, may enable screening for a broad range of nucleotide variations and may prevent less common, population-restricted, novel sequence variants from being overlooked.