STOX1 promotor region -922 T > C polymorphism is associated with Early-Onset preeclampsia.

Preeclampsia (PE), affecting 5-8% of pregnancies, is a common pregnancy disease that has harmful effects on mother and foetus. It has been found that the STOX1 (Storkhead Box 1), which is a transcription factor, carries variants associated with PE. Previous studies showed that, there was a strong relationship between PE and STOX1 variants. Therefore, we hypothesised that variants in the promoter region of the gene may be related to the onset of PE. The aim of this study is to investigate the contribution of STOX1 gene promoter region variants to PE. The blood samples taken from 118 PE patients and 96 healthy pregnant women were analysed by Sanger sequencing method. Sequence analysis results showed that, there is a-922 T > C polymorphism (rs884181) in the promoter region of the STOX1 gene. This polymorphism was found to be statistically significant in individuals with early onset PE (p = 0.02) and in PE (p = 0.014) compared to the control group.IMPACT STATEMENTWhat is already known on this subject? As a result of whole-exon studies on the STOX1 gene, polymorphisms were found to disrupt the structure/expression/function of the gene and strengthen its relationship with PE and HELLP syndrome. A previous study by our team found an association between Y153H, the most common polymorphism of STOX1, and early onset PE.What do the results of this study add? In our study, it was aimed to investigate the effect of genetic modifications in STOX1 gene promoter region on PE through the maternal genotype. Because any change in the promoter region affects the expression level of the gene. Also, for the first time, sequence analysis of the promoter region of STOX1 is investigated in PE. The variations in STOX1 appear to be important in PE especially in Early Onset PE.What are the implications of these findings for clinical practice and/or further research? Although PE is a disease that occurs with pregnancy and shows its effects most during this period, women and children with a history of PE are more prone to various disorders, especially cardiovascular diseases in the following years. Therefore, understanding the pathogenesis of the disease is important for both prevention and treatment process. Variations on STOX1 appear to be important in terms of disease risk.

The role of two common FOXP3 gene promoter polymorphisms in preeclampsia in a Turkish population: a case-control study.

Preeclampsia (PE), which occurs in approximately 5% of pregnancies worldwide and constitutes clinically serious complications in 2-3%, is one of the leading causes of maternal and prenatal morbidity and mortality. Recent studies report that regulatory T (Treg) cells, which act as immunosuppressant, are associated with PE. It is clearly defined that FOXP3/Scurfin (Forkhead Box P3) is involved in the development and function of Tregs. However, there are different conclusions regarding the relationship between PE and FOXP3 gene polymorphisms for different populations. For this reason, in this study we investigate the association between FOXP3 gene promoter region polymorphisms and PE in a Turkish population 500 PE patients and 500 healthy pregnant women. Blood samples taken from pregnant women were studied by PCR-RFLP method. As a result, rs2232365 polymorphism was significantly associated with disease (p < .0001) while no significant association was found between rs3761548 polymorphism and the disease (p = .17). Based on these results, it is though that FOXP3 rs2232365 polymorphism may be predisposed to PE development in terms of Turkish population. However, further and functional studies are needed in terms of other polymorphisms and mutations.IMPACT STATEMENTWhat is already known on this subject? A number of recent publications suggest that Tregs may play a role in the pathogenesis of PE. It is known that a stable and high FOXP3 expression is required to maintain the suppressive T cell function of Tregs. Down regulation of FOXP3 in PE has been reported in many previous studies, but the mechanism is still uncertain.What do the results of this study add? Our study has examined two FOXP3 promoter region polymorphisms in terms of Turkish population for the first time. Rs2232365 polymorphism associated with the disease in heterozygous genotype.What are the implications of these findings for clinical practice and/or further research? It has been shown that FOXP3 gene promoter region polymorphisms may be associated with PE for Turkish population. Our results can be a guide for more detailed statistical evaluations and functional studies.

Dysregulated Leukotriene Metabolism in Patients with COVID-19.

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

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.

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

BACKGROUND: Arachnoid 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: We 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.

Fibroblast growth factor receptor 4 Gly388 Arg 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) Gly(388) Arg polymorphism and pre-eclampsia (PE) by carrying out a case-control study in Turkish women. MATERIALS AND METHODS: In the present study 159 PE patients and 161 controls were included. DNA was extracted from peripheral blood leukocyte and FGFR4 Gly(388) Arg polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: For Gly388Arg polymorphism of FGFR4 we found no significant association between controls and PE patients. The frequencies of GlyGly, GlyArg and ArgArg genotypes were 56.6%, 36.4% and 7% for the study group and 50.3%, 44.7% and 5% for the control group, respectively. The risk of women with the GlyArg (odds ratio = 0.7, 95% confidence interval: 0.45-1.14) and ArgArg (odds ratio = 1.2, 95% confidence interval: 0.47-3.22) genotypes for PE did not differ significantly from that of GlyGly genotype carriers. CONCLUSION: As we could not find any association between genetic variability in Gly(388) Arg of FGFR4 and PE, this specific polymorphism of FGFR4 can be eliminated as a risk factor for PE at least for Turkish women.

Computationally predicted SARS-COV-2 encoded microRNAs target NFKB, JAK/STAT and TGFB signaling pathways.

Recently an outbreak that emerged in Wuhan, China in December 2019, spread to the whole world in a short time and killed >1,410,000 people. It was determined that a new type of beta coronavirus called severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) was causative agent of this outbreak and the disease caused by the virus was named as coronavirus disease 19 (COVID19). Despite the information obtained from the viral genome structure, many aspects of the virus-host interactions during infection is still unknown. In this study we aimed to identify SARS-CoV-2 encoded microRNAs and their cellular targets. We applied a computational method to predict miRNAs encoded by SARS-CoV-2 along with their putative targets in humans. Targets of predicted miRNAs were clustered into groups based on their biological processes, molecular function, and cellular compartments using GO and PANTHER. By using KEGG pathway enrichment analysis top pathways were identified. Finally, we have constructed an integrative pathway network analysis with target genes. We identified 40 SARS-CoV-2 miRNAs and their regulated targets. Our analysis showed that targeted genes including NFKB1, NFKBIE, JAK1-2, STAT3-4, STAT5B, STAT6, SOCS1-6, IL2, IL8, IL10, IL17, TGFBR1-2, SMAD2-4, HDAC1-6 and JARID1A-C, JARID2 play important roles in NFKB, JAK/STAT and TGFB signaling pathways as well as cells' epigenetic regulation pathways. Our results may help to understand virus-host interaction and the role of viral miRNAs during SARS-CoV-2 infection. As there is no current drug and effective treatment available for COVID19, it may also help to develop new treatment strategies.

STOX1 gene Y153H polymorphism is associated with early-onset preeclampsia in Turkish population.

Preeclampsia (PE) is a disease of pregnancy that causes of maternal and prenatal morbidity worldwide. Studies indicate that variations in STOX1 gene may be a direct risk factor to PE but controversial results regarding the relationship of Y153H variation in the second exon of STOX1 gene with PE have been ongoing since 2005. The aim of this study was to identify if there is any correlation between Y153H polymorphisms and PE in Turkish preeclampsia patients. We performed polymerase chain reaction- restriction fragment lengthpolymorphism(PCR-RFLP) analysis in 500 pregnant women, of whom 373 pregnant women with early onset PE (EOPE) and 500 normal pregnant women. The relationship between STOX1 Y153H polymorphism and EOPE/LOPE was evaluated by statistical analysis. We found that STOX1 Y153H polymorphism is a risk factor for EOPE (p = 0.03). The odds ratio was 1,45 (CI 95% = 1,03-2,05). No relationship between STOX1 Y153H polymorphisms and LOPE (p = 0.13) was found. STOX1 gene Y153H polymorphism is associated with the risk ofearly onset of pre-eclampsiain a Turkish population. The results provide further evidence of the role of STOX1 in the pathophysiology of this disease.

Decreased FENDRR and LincRNA-p21 expression in atherosclerotic plaque.

OBJECTIVE: Cardiovascular diseases are the most important cause of mortality worldwide, particularly atherosclerosis. Recently, lncRNAs affecting atherosclerotic progression have been reported in vascular smooth muscle cells, endothelial cells, and monocytes, suggesting that lncRNAs play an important role in atherosclerosis. METHODS: In recent clinical studies, nowadays, it was determined that internal mammary bypass grafts are closest to ideal grafts in coronary artery bypass surgery. In this study, we used tissue samples taken from atherosclerotic coronary arteries and the internal mammary artery (IMA) during coronary artery bypass surgery. Using RT-PCR, we investigated the role of two lncRNAs, FENDRR and LincRNA-p21, by comparing their expression levels in coronary artery plaques and normal mammary arteries of 20 atherosclerotic patients. RESULTS: We found that the FENDRR and LincRNA-p21 expressions decreased by approximately 2 and 7 fold in coronary artery plaques, respectively, compared with those in IMA, which is known to have no plaque development. CONCLUSION: This study was the first to use mammary artery tissues of the same patients as a control and to study FENDRR expression. Our data may provide helpful insights regarding the association of lncRNAs and atherosclerosis.

FOXP3 rs3761548 polymorphism is associated with knee osteoarthritis in a Turkish population.

AIM: Functional polymorphisms located in FOXP3 intron 1 was recently found to be associated with rheumatoid arthritis (RA). Although RA is an autoimmune disease, there is supporting evidence that activated maladaptive responses including pro-inflammatory pathways play roles in osteoarthritis (OA), similar to RA. The aim of this study was to explore the relationship between rs2232365 (-924A/G) and rs3761548 (-3279A/C) polymorphisms as well as possible changes in the 600 bp promoter region of FOXP3 and knee OA. METHODS: Patients with primary knee OA (n = 300) and healthy individuals (n = 300) were examined for rs3761548 and rs2232365 FOXP3 gene polymorphisms by the polymerase chain reaction-restriction fragment-length polymorphism method. The 600 bp promoter region (between -500 and +100) of the gene was also sequenced with direct sequencing in 50 knee OA patients and 50 healthy individuals. RESULTS: There were no sequence variants in the promoter region tested both in OA patients and healthy controls. The SNP rs2232365 showed no association with OA susceptibility and severity and the results of other genetic models were also nonsignificant. On the other hand, rs3761548 AC (P = 0.003), AA + CC (P = 0.0014) as well as AC + AA (P = 0.40) genotypes showed association with Grade 4 knee OA patients. CONCLUSION: Our findings indicated that the association between FOXP3 rs2232365 polymorphism and knee OA tended to yield negative results but the FOXP3 rs3761548 C allele was associated with elevated risk of OA in Grade 4 knee OA patients in a Turkish population.

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.

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.

Lack of association between the CYP11B2 gene polymorphism and preeclampsia, eclampsia, and the HELLP syndrome in Turkish women.

OBJECTIVES: It is possible that altered control of aldosterone synthase gene (CYP11B2) expression or translation may be responsible for hypertension. Hypertension is one of the major components of preeclampsia. We present here a study investigating the association between the CYP11B2 gene polymorphism in the promoter region at the position of -344 and preeclampsia. STUDY DESIGN: We analyzed a group of Turkish women for preeclampsia (n=143), eclampsia (n=36), and the HELLP syndrome (n=55) and compared them with controls (n=147). Genotypes for CYP11B2 were determined by polymerase chain reaction followed by digestion with BsuRI restriction enzyme. RESULTS: The -344T/T, -344C/T, and -344C/C genotypes were found at comparable frequencies among the study groups, between the study and control groups, and between the study groups combined and the control group (p>0.05). We combined the genotypes of TC and CC (polymorphic) and compared them with the TT (wild-type) genotype. There was no significant difference in the frequency of the TC plus CC genotypes among the study groups, between the study and control groups, and between the study groups combined and the control group (p>0.05). There was no association of the CYP11B2 polymorphism among the preeclampsia, eclampsia, and HELLP groups and controls. CONCLUSIONS: The CYP11B2 gene polymorphism is not directly associated with preeclampsia, eclampsia, and the HELLP syndrome in women with these conditions. Therefore, this polymorphism may not be a risk factor for these disorders, at least not in the Turkish population.

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.

Recombinant alpha and beta subunits of M.AquI constitute an active DNA methyltransferase.

AquI DNA methyltransferase, M.AquI, catalyses the transfer of a methyl group from S-adenosyl-L-methionine to the C5 position of the outermost deoxycytidine base in the DNA sequence 5'CYCGRG3'. M.AquI is encoded by two overlapping ORFs (termed alpha and beta) instead of the single ORF that is customary for Class II methyltransferase genes. The structural organization of the M.AquI protein sequence is quite similar to that of other bacterial C5-DNA methyltransferases. Ten conserved motifs are also present in the correct order, but only on two polypeptides. We separately subcloned the genes that encode the alpha and beta subunits of M.AquI into expression vectors. The overexpressed His-fusion alpha and beta subunits of the enzyme were purified to homogeneity in a single step by Nickel-chelate affinity chromatography. The purified recombinant proteins were assayed for biological activity by an in vitro DNA tritium transfer assay. The alpha and beta subunits of M.AquI alone have no DNA methyltransferase activity, but when both subunits are included in the assay, an active enzyme that catalyses the transfer of the methyl group from S-adenosyl-Lmethionine to DNA is reconstituted. We also showed that the beta subunit alone contains all of the information that is required to generate recognition of specific DNA duplexes in the absence of the alpha subunit

AXIN2 polymorphism and its association with prostate cancer in a Turkish population.

Polymorphism of AXIN2, a component of Wnt signaling, has been shown to play a role in tumorigenesis and dysregulated in cancer cells. In order to find out if AXIN2 polymorphism is a risk factor for prostate cancer, we analyzed eight polymorphic regions of this gene in 84 patients with prostate cancer and compared the results with 100 healthy controls in a Turkish population using PCR-RFLP methods. The genotype frequencies and risk factors of prostate cancer and control groups were analyzed by Chi-square test. We found a statistically significant result between prostate cancer risk and AXIN2 Intron2-956+16A/G (rs35285779) SNP. The frequency of the homozygous G/G (0%) and heterozygous A/G (18%) genotypes was significantly less in patients with prostate cancer than in healthy controls (7 and 32%, respectively) (P<0.05) for this SNP. When compared with the wild-type A/A genotype of the controls, prostate cancer patients with the A/G and G/G genotype showed reduced risk of cancer; the adjusted odds ratio (OR) for patients with the homozygous G/G genotype was 0.87 (95% CI: 0.81-0.95) and for heterozygous A/G genotype was 0.42 (95% CI: 0.20-0.85). We found no statistically significant association between controls and prostate cancer for other seven SNPs of AXIN2 including Exon1-148 C/T (rs2240308), Exon1-432 T/C (rs2240308), Exon5-1365 G/A (rs9915936), Exon5-1386 C/T (rs1133683), Intron5-1712+19 T/G, Exon7-2062 C/T, and Intron7-2141+73 G/A (rs4072245) (P>0.05). These results suggest that the AXIN2 Intron2 rs35285779 SNP is associated with development of prostate cancer as a protective SNP, while an association between other seven SNPs of the AXIN2 and risk of prostate cancer was not observed.

Microsomal epoxide hydrolase polymorphisms.

Microsomal epoxide hydrolase plays a dual role in the activation and detoxification of carcinogenic compounds. Two polymorphic sites have been described in exons 3 and 4 of the microsomal epoxide hydrolase gene that change tyrosine residue 113 to histidine (Tyr113His) and histidine 139 to arginine (His139Arg), respectively. The exon 3 polymorphism reduces enzyme activity by approximately 50%, whereas the exon 4 polymorphism causes a 25% increase in activity. In the present study, the distribution of these polymorphisms in a Turkish population including 625 unrelated healthy individuals was examined using a PCR-RFLP method. The observed genotype frequencies of microsomal epoxide hydrolase exon 3 were 54, 38 and 8% for Tyr113Tyr, Tyr113His and His113His, respectively. Exon 4 genotype frequencies were found to be 69, 29 and 2% for His139His, His139Arg and Arg139Arg, respectively.

AXIN2 polymorphism and its association with astrocytoma in a Turkish population.

The product of AXIN2, a component of Wnt signalling, plays a role in tumorigenesis and is dysregulated in cancer cells. In order to determine whether the AXIN2 polymorphism is a risk factor for astrocytoma, we analysed eight polymorphic regions of this gene in 100 astrocytoma patients compared to 100 healthy controls in a Turkish population using PCR-RFLP methods. For the Exon1-148 T/C, Exon1-432 C/T, Exon5-1365 G/A, Intron5-1712+19G/T, Exon7-2062 C/T and Intron7-2141+73 G/A SNPs of AXIN2, no significant association between controls and astrocytoma patients was found. For the Exon5-1386 C/T SNP, a statistically significant association between controls and patients was found (p<0.05). For this astrocytoma, patients with the TT genotype showed an increased risk with an OR of 2.92 (adjusted for age, gender and smoking status) (95% CI 1.14-7.47) as compared to the controls with the CC genotype. Our results suggest that AXIN2 SNPs may be associated with astrocytoma.

Strong association between lung cancer and the AXIN2 polymorphism.

Accumulated evidence suggests that alterations due to mutations or genetic polymorphisms in the AXIN2 tumor suppressor gene, a component of the Wnt signaling pathway, contributes to carcinogenesis. The effect of the AXIN2 exon 1 148 C↷T polymorphism was recently investigated in a Japanese population, but has not been investigated in other populations. Additionally, other common polymorphisms of this gene have not been studied. In the present study, 8 polymorphisms of the AXIN2 gene, including exon 1 148 C↷T, were investigated in a Turkish population of 100 lung cancer patients using PCR-RFLP methods. For the exon 1 432 C↷T, exon 5 1365 G↷A, exon 5 1386 C↷T, intron 5 1712+19 G↷T, exon 7 2062 C↷T and intron 7 2141+73 G↷A single nucleotide polymorphisms of AXIN2, no significant association was found between the controls and the lung cancer patients. For exon 1 148 C↷T, a statistically significant association between the controls and lung cancer patients was found. For this region, lung cancer patients with the TT genotype showed a decreased risk [odds ratio (ORTT) 0.33, 95% confidence interval (CI) 0.12-0.89; p=0.032 (adjusted for age, gender and smoking status)] as compared with the controls with the CC genotype. Concerning histological tumor type, it has been found that exon 1 148 C↷T SNP is associated with a significant decreased risk in squamous cell carcinoma patients (ORTT 0.16; 95% CI 0.03-0.79; p=0.014). Male (ORTT 0.19; 95% CI 0.04-0.77; p=0.015) and smoker (ORTT 0.11; 95% CI 0.01-0.71; p=0.019) lung cancer patients with the TT genotype showed a decreased risk for the same region. Our results suggest that the risk of lung cancer in a Turkish population is related to polymorphisms of the AXIN2 gene.

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. METHODS: DNA was extracted from peripheral blood leukocytes, and genotype distribution of exon 3 and exon 4 of epoxide hydrolase gene (EPHX) was carried out in 271 patients and 155 controls. RESULTS: There was no statistically significant difference in the distribution of genotypes between pre-eclampsia without HELLP and pre-eclampsia plus HELLP cases and controls for the exon 3 and 4 polymorphism of EPHX. However, we found a significant association between the predicted enzyme activity level and pre-eclampsia (P = 0.018). The distribution of subjects with predicted high, intermediate and low microsomal epoxide hydrolase enzyme (EPHX) activity were 23.2, 38.8 and 38% in cases and 12, 47.3 and 40.7% in controls, respectively. CONCLUSION: Although we could not find any association between genetic variability in exon 3 and 4 of EPHX and pre-eclampsia, genetic variability in these two exons jointly modifies the predicted enzyme activity and may be a risk factor for pre-eclampsia.