Ergun Pinarbasi

Strong association between the GSTM1-null genotype and lung cancer in a Turkish population

Glutathione S-transferases are possibly related to the detoxification of many xenobiotics involved in the etiology of cancer. To investigate the role of the glutathione S-transferase M1 deletion (GSTM1-null) in lung cancer, the polymerase chain reaction was used to determine the GSTM1 genotypes of lung cancer patients (n=101) and hospital (n=206) in a Turkish population. The prevalence of the GSTM1-null genotype in the case group was 48%, compared to 18% in the control group, giving an odds ratio (OR) of 4.14 (95% confidence interval [CI]=2.36-7.27). The analysis of patients by histologic type of lung cancer (10% adenocarcinoma, 43% squamous cell carcinoma, 26% small cell carcinoma, and 11% large cell carcinoma) showed no association between histopathologic type of lung cancer and GSTM1-null genotype. When the interaction between the GSTM1-null genotype and smoking status was analyzed, among the 67 smokers, the GSTM1-null genotype was found in 37 (55%) with an OR of 2.58 (95% CI=1.00-6.73) indicating a significant association. However, no association was found between smoking exposure (<30 and > or =30 packs/year) and GSTM1-null genotype. We conclude that, in this study the null GSTM1 genotype is an independent risk factor for the development of lung cancer for Turkish population.

Association of microsomal epoxide hydrolase gene polymorphism and pre‐eclampsia in Turkish women

Aim:  To assess the association between human epoxide hydrolase exon 3 and 4 polymorphisms and pre‐eclampsia by carrying out a case‐control study in Turkish women.

A Novel Locus for Restless Legs Syndrome on Chromosome 13q

Background: Restless legs syndrome (RLS) is a sensorimotor disorder in which affected individuals suffer from uncomfortable sensations and an urge to move their lower limbs; it occurs mainly in resting situations during the evening or at night. Multiple chromosomal loci have been mapped for RLS through family-based linkage analysis, and genome-wide association studies but causative mutations have not been identified yet. Method: We identified an RLS family from the eastern part of central Turkey which has 10 patients suffering from this syndrome. Whole genome linkage analysis was performed in family members who consented for study (9 affected and 2 unaffected). Results: A theoretical maximum logarithm of the odds score of 3.29 was identified at chromosome 13q32.3–33.2. This result shows strong genetic linkage to this locus. Conclusions: We demonstrated a genetic linkage at chromosome 13 in a RLS family. Further investigation in this linkage area may reveal a causative gene leading to RLS phenotype and may illuminate the pathogenesis of this disease. This study supports the genetic heterogeneity in the pathogenesis of this syndrome.

No association of polymorphisms in the glutathione S-transferase genes with pre-eclampsia, eclampsia and HELLP syndrome in a Turkish population

Aim: There is substantial evidence that genetic factors play a role in pre‐eclampsia. The aim of this study was to determine whether genetic variability in the encoding of genes for glutathione S‐transferase M1 (GSTM1) and glutathione S‐transferase T1 (GSTT1) contributes to individual differences in susceptibility to pre‐eclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome).

Intracranial arachnoid cyst family with autosomal recessive trait mapped to chromosome 6q22.31-23.2.

BackgroundArachnoid cysts are congenital fluid-filled compartments within the cerebrospinal fluid cisterns and cerebral fissures. They most commonly occur sporadically, and familial occurrence has rarely been reported. In this study, we showed the first genetic linkage in the literature in a pure intracranial arachnoid cyst family with autosomal recessive trait.MethodsWe identified an intracranial arachnoid cyst family in southern Turkey whose six of seven offspring had intracranial arachnoid cysts in different localizations, and collected venous blood from seven offspring of the family. Whole-genome linkage analysis was performed in all offspring.ResultsA theorical maximum logarithm of the odds score of 4.6 was identified at chromosome 6q22.31-23.2. This result shows strong genetic linkage to this locus.ConclusionsWe present the first genetic linkage analysis result in a pure intracranial arachnoid cyst family in literature. Further investigation of this linkage area can reveal a causative gene causing the intracranial arachnoid cyst phenotype and can illuminate the pathogenesis of this disease.

MEFV mutations and their relation to major clinical symptoms of Familial Mediterranean Fever

Familial Mediterranean fever is a common hereditary disease in Turkey. To date, different mutational spectrum of MEFV gene was observed in studies carried out in different regions of Turkey but in most of these studies association of clinical symptoms of FMF to mutant genotypes have not been investigated in details. Here we report the MEFV gene variations in exons 2, 3, 5 and 10 and their relations to major clinical symptoms of FMF in 514 unrelated (245 males and 269 females) Turkish patients. MEFV mutations were found in 45% (n=230) of patients and 55% (n=284) of patients did not have any mutations. One hundred and thirty-seven (60%) patients were heterozygous, 57 (24.7%) patients were compound heterozygous, 33 (14%) patients were homozygous and 3 (1.3%) patients were having a complex genotype. Allele frequencies of MEFV mutations were M694V (48%), E148Q (18%), M680I (15%), V726A (12.5%), P369S (3.3%), R761H (0.9), K695R (0.9), E148V (0.9) and A744S (0.5%). Abdominal pain (76%) and fever (58%) were two most seen complications among patients followed by arthritis (28%) and chest pain (19%). Almost all major clinical symptoms of FMF were higher in patients with one or more M694V or M680I mutant allele. In contrast, patients having E148Q or V726A mutant allele showed fewer clinical FMF symptoms. Patients with P369S have higher abdominal pain, chest pain and fever than expected. Arthritis was high in K695R heterozygous genotype. One hundred and eighteen patients were carrying more than one polymorphic allele. The most common polymorphism was R202Q (13%). In addition, a novel heterozygous polymorphism at 564th nucleotide (C>T) of exon2 were found in 2 patients.

Association between the soluble epoxide hydrolase gene and preeclampsia

ABSTRACT Objective: In this study the association between K55R polymorphism, methylation level of the EPHX2 promoter region, and PE was investigated in 520 individuals including 260 PE patients and 260 healthy pregnant women. Methods: K55R polymorphism and methylation level of the EPHX2 promoter were determined by the real-time PCR using double-dye hydrolysis probes and methylation-sensitive high-resolution melting analysis, respectively. Results: The presence of the K55R polymorphism was significantly higher in cases (28.1%) than controls (17.3%), and was associated with increased risk of PE (OR: 1.86; 95% CI: 1.09–2.63). Methylation levels of the EPHX2 promoter region in cases were significantly lower than controls. A 2.83 times increased PE risk was observed in pregnant women with EPHX2 promoter methylation levels of <25% (OR: 2.83; 95% CI: 1.15–6.91). Conclusion: In conclusion, hypomethylation of the promoter region of EPHX2 and K55R polymorphism were associated with significant increased risk of PE. sEH enzyme may play a role in the pathogenesis of PE by contributing to reduction of the vasodilatator, anti-hypertensive, and anti-inflammatory effects of EETs by rapid degradation of these molecules.

Fibroblast growth factor receptor 4 Gly388Arg polymorphism is not associated with pre-eclampsia in Turkish women

Aim:  The aim of this study was to assess the association between human fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism and pre‐eclampsia (PE) by carrying out a case–control study in Turkish women.