Relationship between MCP1 (-2518A>G) gene variants and ovarian cancer in Turkish population.

The monocyte chemoattractant protein-1 (MCP-1) gene polymorphism(-2518A>G)  in the regulatory region of the MCP-1 protein has been reported to be associated with cancer risk. In this study we aimed to investigate the relationship of MCP-1 (-2518A>G) gene polymorphism and ovarian cancer. MCP-1 genotyping was performed using polymerase chain reaction from blood samples ofovarian cancer patient (n=56) and a control groups (n=52).There was a significant difference in MCP1 (-2518A>G) genotypes between the patient and control groups (p=0.049; x2=6.042). AA carriers were significantly higher in the control group (p=0.014) whereas AG genotype and G allele carriers were significantly higher in the ovarian cancer group (p=0.029, p=0.014, respectively). This study suggests that MCP-1 (-2518A>G) AG genotype and G allele could be considered as risk factor for susceptibility to ovarian cancer.

Effects of genetic factors to stent thrombosis due to clopidogrel resistance after coronary stent placement.

Stent thrombosis (ST) is considered as a multifactorial problem which is mostly occurs due to clopidogrel resistance. It may be due to some CYP450 enzyme deficiencies which play role in clopidogrel metabolism. Therefore the aim of this study is to detect the mutations in CYP2C19 and CYP2C9 genes which may cause ST, and to investigate the relation between other risk factors and ST. 50 individuals who have stent thrombosis and 50 individuals who haven't got any complication were enrolled as patient and control group respectively. *2,*3,*4,*5,*17 mutations in CYP2C19 gene and *2 ve *3 mutations in CYP2C9 gene were investigated with RT-PCR. Clopidogrel and aspirin resistance were investigated with multiple electrode platelet aggregometry. Results were evaluated statistically. CYP2C19*2 mutation was found statistically higher in patients (% 18), whereas CYP2C19*17 was found statistically higher in controls (% 36)(p<0.05). Additionally, it was found that patients who have clopidogrel and/or aspirin resistance also have CYP2C19*1/*2 or CYPC19*2/*2 genotype. These relations were also found statistically significant. (p=0,000005 for clopidogrel resistance and p=0,000059 for aspirin resistance). In conclusion, it was suggested that there is a relation between CYP2C19*2 mutations and ST due to clopidogrel resistance, and CYP2C19*17 may have a protective role in this process. The use of novel and more potent drug or high clopidogrel maintenance dosing before stent implantation may be beneficial treatment options for antiplatelet therapy in CYP2C19*2 carriers.

Effects of PAX9 and MSX1 gene variants to hypodontia, tooth size and the type of congenitally missing teeth.

ooth agenesis, affecting up to 20% of human population, is one of the most common congenital disorder. The most frequent form of tooth agenesis is known as hypodontia, which is characterized by the absence of one to five permanent teeth excluding third molars. It was considered that hypodontia is especially related with gene mutations which play role in tooth formation. Additionally mutations in PAX9 and/or MSX1 have been identified as the defects responsible for missing permanent molars and second premolars. In some studies it was also found that PAX9 and MSX1 gene mutations may change tooth size. Therefore  in this study all of these factors were investigated. Thirty one patients and 30 controls were enrolled to the study. Information about tooth sizes and type of congenitally missing teeth were collected. MSX1 and PAX9 gene mutations were investigated by direct sequencing. Results were evaluated statistically. As a result, 22 variations were detected in PAX9 in which 18 of them are novel. In addition, 7 variations were found in MSX1 in which 5 of them are novel and one of them lead to amino acid change. Statistically significant relations were found between detected variations and tooth sizes. Any relation between mutations and type of congenitally missing teeth were not detected. In conclusion, especially new mutations which may cause hypodontia, effect tooth size and type of congenitally missing teeth, should be investigated with other researchers for clarifying the mechanism.

Investigation of some DNA repair genes association in non small cell lung cancer.

Ribonucleoside-diphosphate reductase subunit M2, also known as ribonucleotide reductase small subunit, is an enzyme that in humans is encoded by the RRM2 gene and also Ribonucleoside-diphosphate reductase large subunit is an enzyme that in humans is encoded by the RRM1 gene. RRM1 is a gene important in determining tumor phenotype, but also induced the expression of PTEN tumor suppressor gene, cell migration, invasion and metastasis formation, and play a preventive role. ERCC2 DNA repair mechanism is associated in more than 20 genes involved in the NER pathway. The aim of this study is to investigate rs13181 ERCC2 (T>G) (Lys751Gln), rs12806698 RRM1 (-269C>A) and rs6759180 (located in the 5'UTR) RRM2 (10126436G>A) gene polymorphisms by using real time PCR technique in patients with NSCLC. 193 NSCLC cases and 141 healthy control cases were included in this study. A significant difference was found between rs12806698 RRM1 genotype distributions (*p: 0.034) and were determined increases the risk of disease approximately 3.044 times AA genotype having (*p: 0.014 OR: 3.044, 95%CI: 1.205-7,688). A significant difference was found between rs6759180 RRM2 genotype distributions (*p: 0.033) and were determined increases the risk of disease approximately 3.49 times GG genotype having (p: 0,009 OR: 3, 49, %95CI:1.291-9,482). It was found significant difference in serum 8-OHdG levels between patients and controls (*p: 0001).

An association between MPO -463 G/A polymorphism and type 2 diabetes.

Myeloperoxidase (MPO) is an enzyme which is a member of the haem-peroxidase superfamily and plays a role in production of reactive oxygen species. The most common polymorphism in the promoter region of MPO gene is -463 G/A. It was shown that carrying the GG genotype means increased activity of the gene approximately 2-3-fold compared to GA and AA genotypes. It was found that hyperglycaemia, modified oxidized proteins and increased advanced glycosylated end products (AGE) are related to oxidative stress in diabetes. Under the hyperglycaemic conditions, production of reactive oxygen radical is elevated in smooth muscle endothelial cells, mesengial and tubular endothelial cells. Especially, elevated lipid oxidation plays an important role in pathogenesis of diabetic complications such as cardiovascular complications. We examined the MPO -463 G/A polymorphism by using the PCR-RFLP method in 145 type 2 diabetic patients and 151 healthy controls. We observed that the AA genotype and A allele were protective variants against type 2 diabetes and the GG genotype was a risk factor for diabetes. While we studied the relationship between genotypes and biochemical parameters, we found that patients with the A allele had decreased serum cholesterol, triglyceride, VLDL levels and body mass index. We suggest that the MPO gene has an important role in pathogenesis of type 2 diabetes because of the increased frequency of GG genotype, which is related to increased activity and oxidant capacity of MPO in the patients.

Expression levels of elastin and related genes in human varicose veins.

Among the suspected reasons for varicose vein formation are changes in the quantity and content of the elastin protein; however, comprehensive investigations about elastin assembly in varicose vein formation are yet lacking. In this study, we aimed to determine the changes in mRNA levels of elastin and some of its functionally related proteins, fibulin 5, LOXL-1, MMP-2 and MMP-9 in varicose vein formation. We analysed the mRNA levels of elastin, fibulin-5, LOXL1, MMP2 and MMP9 in samples of 35 healthy and 35 varicose great saphenous vein tissues. mRNA levels of these genes were determined by using real-time PCR and normalized with HPRT1. When we compared the patient and control groups, elastin mRNA levels were significantly higher in the patient group than in the control group (P = 0.047), although there were no significant differences in fibulin 5, LOXL1, MMP2 and MMP9 mRNA levels between the patient and control groups. We showed that up-regulation of MMP2 mRNA expression was significantly correlated with hyperlipidaemia (P = 0.029). The up-regulation of elastin expression may play an important role in the pathogenesis of primary varicose veins. Additionally, the up-regulation of MMP2 expression was strongly correlated with hyperlipidaemia in varicose veins.

Investigation of NF-κB1 and NF-κBIA gene polymorphism in non-small cell lung cancer.

Lung cancer is a complex, multifactorial disease which is the leading cause of cancer death in both men and women. NF-κB is a transcription factor which is known to affect the expression of more than 150 genes related to inflammation, lymphocyte activation, cell proliferation, differentiation, and apoptosis, as well as contributing to cell apoptosis and survival. However, NF-κBIA (IκBα) is the inhibitor of the transcription factor. The--94ins/delATTG polymorphism of the NF-κB1 gene promoter region which causes a functional effect and NF-κBIA 3'UTR A → G polymorphism has been shown to be related to various inflammatory diseases and cancer. Ninety-five NSCLC patients and 99 healthy controls were included in study. The NF-κB1-94ins/delATTG and NF-κBIA 3'UTR A → G polymorphism have been studied by using PCR-RFLP method. It was found that the NF-κB1 -94ins/delATTG DD genotype and D allele frequencies were higher in patients than healthy controls and the presence of the DD genotype has a 3.5-fold increased risk of the disease (P: 0.014). This study is the first to investigate the NF-κB1-94ins/delATTG and NF-κBIA 3'UTR A → G polymorphism together in the Turkish population. According to the results, the NF-κB1-94ins/del ATTG promoter polymorphism may have a role in lung carcinogenesis and prognosis.

Oral squamous cell carcinoma and serum paraoxonase 1.

BACKGROUND: Serum paraoxonase 1 is involved in mechanisms that protect cells from oxidative stress damage. This study aimed to investigate the correlation between serum paraoxonase 1 activity and polymorphisms in patients with oral squamous cell carcinoma. METHODS AND MATERIALS: Fifty-seven patients with oral squamous cell carcinoma and 59 matched healthy controls participated in the study. Serum paraoxonase 1 activity and polymorphisms in blood samples were compared with results for polymerase chain reaction and restriction fragment length polymorphism tests. RESULTS: Mean serum paraoxonase 1 activity levels were lower in patients than controls (mean ± standard deviation, 21.9 ± 5 units/l and 120.4 ± 2 units/l, respectively) (p = 0.001). The serum paraoxonase 1 192 glutamine polymorphism was more common in patients than controls. CONCLUSION: Patients with oral squamous cell carcinoma had significantly lower serum paraoxonase 1 activity levels and a greater prevalence of the serum paraoxonase 1 192 glutamine allele, compared with controls. Serum paraoxonase 1 may play a role in the aetiology of oral squamous cell carcinoma.

Cox-2 gene polymorphism and IL-6 levels in coronary artery disease.

Coronary artery disease is one of the leading causes of mortality and diabetes mellitus is one of its main risk factors due to microvascular and macrovascular complications, such as atherosclerosis. Atherosclerosis is now known to be an inflammatory process mediated by prostaglandins and several interleukins. As both are important in inflammatory processes, we examined Cox-2 (-765G > C) polymorphism and interleukin-6 levels in coronary artery disease patients compared to healthy controls. We also divided the patients into diabetic and non-diabetic groups to check the effects of diabetes mellitus separately. We found that the GG allele frequency was significantly higher in the patient group. Patients with the GG genotype had an approximately 2.78-fold higher risk of coronary artery disease. We also found that the Cox-2 (-765G > C) polymorphism is associated with lower interleukin-6 levels, which decreased in the order: GG > GC > CC.

CCR2-64I is a risk factor for development of bladder cancer.

Chemokines are potent proinflammatory cytokines that are implicated in numerous inflammatory diseases. Proinflammatory gene polymorphisms lead to variations in the production and concentration of inflammatory proteins. We investigated a possible association between polymorphisms in chemokine and chemokine receptor genes (MCP-1 A-2518G and CCR2-V64I) and bladder cancer risk. Genotypes were determined by PCR-RFLP assays in 72 bladder cancer patients and 76 unrelated age-matched healthy controls. There were significant differences in the frequencies of the MCP-1 A-2518G (P = 0.012) and CCR2-V64I genotypes (P = 0.004) between the controls and patients. The MCP-1 A-2518G GG genotype frequencies for controls and cases were 0.039 and 0.11, respectively; individuals who had the GG genotype had a 3-fold increased risk of bladder cancer (P = 0.08). The CCR2-64I/64I genotype frequencies for controls and cases were 0.02 and 0.13, respectively; subjects carrying the 64I/64I genotype had a 5.9-fold increased risk of bladder cancer compared to the other genotypes. Individuals carrying the CCR2-V64I heterozygote or homozygous variant genotype (64I/64I + wt/64I) had a 2.9-fold increased risk of bladder cancer compared with the wild-type genotype (wt/wt). CCR2-V64I heterozygote or homozygous wild-type genotype (wt/wt + wt/64I) frequencies were significantly decreased in the patient group compared with controls. We conclude that CCR2-64I is a new risk factor for bladder cancer.

Association of paraoxonase 55 and 192 gene polymorphisms on serum homocysteine concentrations in preeclampsia.

Paraoxonase 1 (PON1) is thought to influence serum homocysteine concentrations, at least in part, due to its homocysteine thiolactonase activity and to play a role in preeclampsia and atherosclerosis. We investigated the effects of PON 55 and PON 192 polymorphisms on plasma total homocysteine (tHcy) concentrations in preeclamptic and healthy pregnants among Turkish population (N = 106). PON 55 and 192 genotypes were determined by PCR RFLP techniques. Plasma tHcy concentrations were measured by high-performance liquid chromatography. No differences were observed in the distribution of PON 1 55/192 genotypes and allele frequencies between the preeclamptic and healthy pregnants. tHcy level in the plasma of preeclamptic women was found to be increased in comparison with healthy pregnants (P < 0.01). Preeclamptic women bearing the mutated PON 192 RR and wild-type PON1 55 LL genotypes had higher tHcy levels than those of the healthy pregnants with the corresponding genotypes, supporting the possibility that the hyperhomocysteinaemia seen in preeclamptic women is associated with the PON genotypes. However, no influence of the allelic distribution on plasma tHcy concentrations was detected in either group. Our results suggest that PON1 55 and 192 genotypes might have an important role in developing hyperhomocysteinaemia and may also have a role in the pathogenesis of preeclampsia in a Turkish population.

L-myc gene polymorphism and risk of thyroid cancer.

UNLABELLED: L-myc gene polymorphism is a representative genetic trait responsible for an individual's susceptibility to several cancers. However, there have been no reports concerning the association between thyroid cancer and L-myc gene polymorphism. AIM: To analyze the distribution of L-myc gene polymorphism in Turkish patients with thyroid disorders and thyroid cancers. METHODS: We used a molecular genotyping method, polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). We studied 138 patients of whom 47 had multinodular goiter, 13 had follicular cancer and 69 had papillar cancer, in comparison with control group of 109 healthy individuals. RESULTS: No significant difference in the distribution of genotypes was observed between thyroid patients and controls. Carrying SS or LS genotype revealed a 1.96-fold (95% CI 0.573-6.706) risk for the occurrence of follicular cancer when compared with controls, and 3.11-fold (95% CI 0.952-10.216), when compared with multinodular goiter patients (p=0.04). CONCLUSION: We suggest that L-myc genotype profiling together with other susceptibility factors, may be useful in the screening for thyroid nodular malignancy.

Methylenetetrahydrofolate reductase C677T gene polymorphism in osteosarcoma and chondrosarcoma patients.

This study was designed to investigate the association of MTHFR C677T polymorphism and the risk of two common musculoskeletal sarcomas, osteosarcoma and chondrosarcoma. MTHFR genotypes were determined in 56 patients (44 osteosarcoma, 12 chondrosarcoma) and 44 controls using the PCR-RFLP technique. In the gender subgroup analysis, wild-type A allele frequency was higher in male osteosarcoma patients than in male control subjects (P = 0.064). Mutant V allele and mutant VV genotype were similar in the control group compared to the sarcoma groups (P > 0.05). No correlation could be proved between patient tumour site, presence of metastasis, and local tumour relapse and MTHFR polymorphism. The MTHFR C677T polymorphism may not be important in an individual's susceptibility to osteosarcoma and chondrosarcoma in Turkey and may not be a useful marker for identifying patients at high risk of developing sarcomas.

Effects of cholesteryl ester transfer protein TAQ1B polymorphism in renal transplant patients.

BACKGROUND: Dyslipidemia is an important complication in renal transplant patients. Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester between high density lipoproteins and low density lipoproteins. The aim of this study was to investigate CETP Taq1B gene polymorphism and lipid abnormalities in renal transplant patients. METHODS: We studied 29 renal transplant patients and 29 healthy controls. CETP Taq1B polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism techniques. Serum lipid levels were measured enzymatically. Statistical analyses was performed by SPSS for Windows version 7.5. RESULTS: The frequencies of CETP Taq1B B1B1, B1B2, and B2B2 genotypes in patients were 44.8%, 34.5%, and 20.7%; and in control subjects, 37.9%, 37.9%, and 24.2%, respectively. The patients with B1B1 genotype displayed higher levels of total cholesterol (TC), triglycerides, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), and diastolic blood pressure (DBP). (P<.05). Also, patients showing a B1 allele had higher levels of TC, LDL-C, VLDL-C, and DBP compared to healthy controls (P<.05). CONCLUSION: We observed that CETP Taq1B B1 allele and B1B1 genotype have effects on the serum lipid profile among renal transplant patients.

Analysis of L-myc gene polymorphism in patients with renal failure outcome to renal transplant.

BACKGROUND: Abnormalities of cell numbers and apoptosis have been observed in renal failure. As uncontrolled expression of c-myc is known to induce apoptosis, we thought that polymorphism in the other myc gene, L-myc gene, which is structually similar to c-myc and reported to be expressed in the kidney, may have a role in the induction of apoptosis and thus have role in chronic renal failure. The aim of this study was to investigate the relationship between the distribution of L-myc genotypes and renal failure. METHODS: In the present study we examined 101 chronic renal failure patients who had either live or cadaveric renal transplants and 105 healthy individuals, for L-myc gene polymorphism by polymerase chain reactions and restriction fragment length polymorphism techniques. RESULTS: Among our patient group, the distribution of the LL, LS, and SS genotypes was 24% (n=25), 71% (n=71), and 5% (n=5), respectively, versus 41% (n=43), 47% (n=49), and 12% (n=13) in our control group. The distribution of genotypes was significantly different between our patients and the control group (chi2=12.281; P=.002). The frequency of the S allele was significantly higher in the patient group (chi2=6.122; P=.013). CONCLUSION: Our study showed that having an S allele in the L-myc gene may increase the risk of renal failure.

Paraoxonase (PON1) 55 and 192 polymorphism and its effects to oxidant-antioxidant system in turkish patients with type 2 diabetes mellitus.

Paraoxonase (PON1) is a serum enzyme with an antioxidant function, protecting the low density lipoproteins (LDL) from oxidative modifications. Because diabetic patients are at greater risk of oxidative stress, we investigated the effect of PON1 55 methione (M)/leucine (L) and PON1 192 glutamine (A)/arginine (B) polymorphisms on oxidant-antioxidant system in 213 individuals with type 2 diabetes mellitus and 116 non-diabetic control subjects from Turkish population were included in the study. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the PON1 genotypes. Thiobarbituric acid reactive substances (TBARS), conjugated dienes levels in the serum and glutathione (GSH) levels in whole blood were measured spectrophotometrically. In both groups PON1 192 AA and PON1 55 MM genotypes had higher TBARS, conjugated dienes levels and lower GSH levels, whereas PON1 192 BB and PON1 55 LL genotypes had lower TBARS, conjugated diene levels and higher GSH level than other genotypes. We thus conclude that PON1 192 BB and PON1 55 LL alleles have protective effect against oxidative stress.

Paraoxonase 192 polymorphism and its relationship to serum lipids in Turkish renal transplant recipients.

BACKGROUND: Cardiovascular disorders are the leading cause of death in patients with chronic renal insufficiency. Paraoxonase (PON1) gene variants have been identified as risk factors for cardiovascular disease (CVD). METHODS: We investigated the effect of PON1 192 polymorphisms on serum lipid profiles in 29 renal transplant recipients and 26 control subjects. Distribution of the PON1 192-gene polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum lipid levels were measured enzymatically. RESULTS: Frequencies of PON1 192 AA, BB, and AB genotypes among the renal transplant recipients were 38.5%, 26.9%, and 34.6%, and among control subjects they were 35.75%, 17.9%, 46.4%, respectively. The genotype distribution for the PON1 192 polymorphism was not different between the two groups (P = NS, chi-square test). The PON1 192 polymorphisms failed to consistently influence the serum lipid profiles in renal transplant recipients. CONCLUSION: We have shown that the 192 polymorphism of the PON1 gene is not associated with increased cardiovascular risk in renal transplant recipients.

Cholesterol ester transfer protein, apolipoprotein E and lipoprotein lipase genotypes in patients with coronary artery disease in the Turkish population.

The aim of this study was to compare patients with coronary artery disease (CAD) to healthy objects, in order to explore a possible association between CAD and the variants in the gene encoding cholesterol ester transfer protein (CETP), apolipoprotein E (Apo E) and lipoprotein lipase (LPL). The relationship between CETP MspI, apo E and LPL PvuII gene polymorphisms and serum lipids were investigated in 173 patients with CAD and 111 healthy controls. The frequency of Apo epsilon4 (p < 0.05) and CETP M1 (p < 0.01) alleles were higher in the CAD group than in the control group. In the CAD group, those with the Msp M1 allele had higher levels of total cholesterol (TC) (p = 0026) and low-density lipoprotein cholesterol (LDL-C) than those with the Msp M2 allele. Subjects with an epsilon2 allele had the lowest levels of TC and LDL-C, while subjects with the epsilon4 allele had the highest. In the control group, CETP, the Msp M2 allele was associated with a higher level of high-density lipoprotein cholesterol (HDL-C) (p = 0.012) than the Msp M1 allele. The distributions of LPL genotype and allele did not differ between the CAD and control groups. The present study demonstrates that the CETP Msp1 and Apo E gene polymorphisms are associated with variations in lipids in patients with CAD and healthy controls in Turkish population.

Is there additional effect of MTHFR C677T mutation on lipid abnormalities in renal allograft recipients?

BACKGROUND: The MTHFR C677T mutation and elevated atherogenic lipoprotein levels are known as cardiovascular risk factors in patients with renal transplantation treated with cyclosporine (CsA). The aim of the present study was to eveluate the contribution of MTHFR C677T mutation to the risk of dyslipidemia in renal transplant recipients. We also studied the effect of the MTHFR-C677 T genotype on transplant survival. METHODS: The study included 29 nondiabetic renal transplant recipients and 27 healthy controls. MTHFR C677T genotypes were determined by PCR and RFLP techniques. Biochemical parameters were measured in a computerized autoanalyzer. RESULTS: In the patient group, the distribution of the CC, CT, and TT genotypes was 44.8% (n = 13), 37.9% (n = 11), and 17.2% (n = 5), respectively. The frequencies of the C and T alleles were 0.64 and 0.36, respectively. Subjects with the T allele had the highest levels of TC (P <.05) and LDL-C (P <.05); subjects with the CC genotype had the lowest. CONCLUSIONS: We observed that the MTHFR T allele has an unfavorable effect on serum lipid profile, leading to a rise in the total and LDL cholesterol concentrations. Thus, we believe that MTHFR C allele has a protective effect and MTHFR T allele has a detrimental effect on the serum lipid profile.