Evaluation of the predisposition of serotonin transporter polymorphisms (5-HTTLPR) and complement factor H (CFH) variants to smoking status

Aim: To evaluate the susceptibility of the serotonin transporter-associated polymorphic region (5-HTTLPR) and complement factor H (CFH) gene variants to smoking status. Method: Smokers and non-smokers were included in the study. The smoking amount was assessed based on the scores on the Fagerström Test for Nicotine Dependence (FTND). DNA is extracted from blood samples. 5-HTTLPR and CFH Y402H variants were analyzed by polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP) methods. The results were evaluated statistically. Results: 5-HTTLPR and CFH Y402H genotype and allele distribution did not differ significantly between smokers and non-smokers (p>0.05). There was no deviation from Hardy-Weinberg equilibrium (HWE) for these variants in the groups. Conclusion: Nicotine addiction is a complex phenomenon in which both genetic and environmental factors play a role. The identification of genes that play a role in addiction is important to elucidate the pathogenesis. The results of this study showed that 5-HTTLPR and CFH Y402H variants had no effect on nicotine addiction. However, these results need to be validated in larger sample groups and in different ethnic communities.   &nbsp

The Analysis on the Effects of COMT, DRD2, PER3, eNOS, NR3C1 Functional Gene Variants and Methylation Differences on Behavoiral Inclinations in Addicts through the Decision Tree Algorythm

The aim of this study was to analyze the effects of Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Period Circadian Regulator 3 (PER3), Endothelial Nitric Oxide Synthetase (eNOS), Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) functional gene variants on possible inclinations of the individuals with Substance Use Disorder (SUD) by using decision trees algorithm and to evaluate the similarities with former studies. The decision trees classification was structured by confirming the effects of genetic and epigenetic sequences of gene variants through 10-fold cross-validation under subtitles of the criminal history, continuum of substance use, former polysubstance abuse, attempted suicide, and inpatient treatment. Performance criteria were evaluated with the similarities of former studies’ accuracy, sensitivity, and precision values. The branching structure of gene variants obtained by tree classification is consistent with the studies in the literature. Our study serves to be the first to show that there is a need for further comprehensive studies with data from different ethnic groups to increase the predictive accuracy rates and to state that machine learning may guide in predicting the effect of gene variants on behavior in the future

Effect of cytokine genes in the pathogenesis and on the clinical parameters for the treatment of multiple myeloma

WOS: 000394527000002PubMed ID: 27611810In this study, we aimed to explore the association among gene variants of five cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta 1), interferon gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-10 (IL-10), and clinical parameters and prognosis in patients with multiple myeloma (MM) treated with novel therapeutic drugs in Turkish population for the first time except TNF-alpha. We analyzed five cytokine genes in 113 cases with MM and 113 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer method (PCR-SSP). AG genotype associated with high expression in TNF-alpha gene (-308) variant was found to be significantly higher (p = 0.019), and GG genotype associated with low expression in TNF-alpha gene (-308) variant was significantly lower in MM group as compared with controls (p = 0.012). IFN-gamma (+874) variant TT genotype was increased (p = 0.037), and AA genotype was decreased (p = 0.002) in MM group in contrast to controls. IFN-gamma (+874) T allele was higher inMMpatients compared with controls (OR = 1.985, p = 0.000), while A allele was significantly lower (OR = 0.5037, p = 0.0005). Multivariate analysis revealed that factors associated with 5-year overall survival (OS) were only IPI III (RR = 1.630, p = 0.018) and thrombocytopenia (RR = 2.207, Cox p = 0.021), while 5-year event-free survival (EFS) was associated with IPI III (RR = 1.524, p = 0.022), thrombocytopenia (RR = 2.902, p = 0.002), APSCT treatment (RR = 1.729, p = 0.035), and female gender (RR = 0.435, p = 0.002) with negative prognostic values. Our results suggested that TNF-alpha gene (-308) AG genotype and IFN-gamma (+874) TT genotype and T allele may have a role on MM, while other cytokines were not associated with the risk of MM

The association of MMP-13 rs2252070 with non-small cell lung cancer in the Turkish population

Aim: To evaluate the role of MMP-13 rs2252070 in patients with non-small cell lung cancer (NSCLC) in the Turkish population. Method: A total of 95 NSCLC patients and 94 healthy controls were included in this study. The MMP-13 rs2252070 variant was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results of the analyses were evaluated for statistical significance. Results: There was no G/G homozygous genotype in the patient or control groups. The prevalence of genotypes of A/A and A/G profiles for the MMP-13 rs2252070 variant was 34.7% and 65.3%, respectively, in patients and 46.8% and 53.2%, respectively, in the control group. No significant difference was found between the patient and control groups in terms of MMP-13 rs2252070 genotype distribution and allele frequency (p= 0.091, OR: 0.605, CI 95%:0.337-1.086; p: 0.199, OR: 1.337, CI 95%: 0.858-2.083, respectively). Conclusions: Our results in this study showed no association between MMP-13 rs2252070 and NSCLC. To fully comprehend the mechanisms underlying NSCLC development, more research is required

Genetic variation of myeloperoxidase gene contributes to aggressive periodontitis: A preliminary association study in Turkish population

Abstract. Myeloperoxidase (MPO) is a lysosomal enzyme found in the azurophilic granules of polymorphonuclear leukocytes. It is involved in the defense against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in aggressive and chronic periodontitis. The aim of this study was to explore the association between MPO-463G/A gene polymorphism and aggressive periodontitis (AgP) and chronic periodontitis (CP). The study included 147 subjects. Probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI) were recorded as the clinical parameters. Genomic DNA was obtained from the peripheral blood of 32 subjects with AgP, 25 with CP, and 90 reference controls. We genotyped the MPO-463G/A polymorphism using the PCR-RFLP method. All data were analyzed using SPSS version 13.0 for windows. There were no significant differences between the CP patients and controls regarding MPO-463A/G gene polymorphism either in terms of allele frequency or genotype frequency of MPO-463A/G. However, either in terms of allele frequency or genotype frequency of MPO-463A/G, there were significant differences between the AgP patients and the controls. In conclusion, our data suggest that MPO-463G/A may be associated with increased risk of aggressive periodontitis in Turkish patients

Polymorphisms of the DNA repair gene XPD (751) and XRCC1 (399) correlates with risk of hematological malignancies in Turkish population

Polymorphisms that occur in DNA repair genes affect DNA repair capacity and constitute a risk factor in hematological malignancies. This study, was aimed to investigate whether xeroderma pigmentosum complementation group D (XPD) and x-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms were involved in the susceptibility to different hematological malignancies. The genotype and allele frequencies were obtained by analyzing XPD gene codon 751 in a total of 80 patients and XRCC1 gene codon 399 polymorphism in a total of 100 patients with hematological malignancies and 100 healthy controls. Mean age was 45 (range: 16 to 75) and 46 (range: 16 to 82) in the patients groups and 39.5 (range: 18 to 67) in the control group, respectively. Additionally, distribution of genotypes and alleles were compared in the patient and control groups. In the comparison of genotype and allele frequencies in hematological malignancies and healthy controls, XPD-751Gln variant was arranged and compared according to age and sex and Gln/Gln genotype was reported to be a protector, which was decreased significantly in acute myeloblastic leukemia (AML) (p = 0.042). No relationship was determined between allele frequencies (p = 0.054). In XRCC1-399, it was shown that Gln/Gln genotype was decreased significantly in AML (p = 0.014) plus all hematological malignancies (p = 0.033) and that Gln allele was present at a lower ratio in AML (p = 0.046). The distribution of polymorphism of both genes was not statistically significant in terms of age and sex. In leukemia with early relapse, XPD 751 Lys/Lys genotype was determined at a statistically higher ratio (p = 0.042). In the evaluation of both genes together, a decrease was noted in Gln/Gln + Lys/Gln haplotype frequency in hematological malignancies (p = 0.048). In this study, it was demonstrated that a decrease in Gln/Gln genotype and Gln allele acted as a protector in XPD codon 751 and XRCC1 codon 399 polymorphisms in acute myeloblastic leukemia (AML) and that an increase in Lys/Lys genotype in acute leukemia was associated with early relapse

XRCC4 rs6869366 polymorphism is associated with susceptibility to both nicotine dependence and/or schizophrenia

Background: Oxidative stress induced DNA damage has been assumed to contribute to the etiopathogenesis of schizophrenia (Sch). Smoking prevalence was more common in patients with Sch. The X-ray repair cross-complementation group 4 (XRCC4) gene plays an important role in the repair of DNA double-strand breaks. Objective: The purpose of this study was to investigate whether XRCC4 rs6869366 polymorphism has a relationship both in nicotine dependence (ND) and Sch+ND risk. Methods: One hundred and four patients with Sch+ND, 133 subjects with ND only and 70 healthy controls were enrolled in the study. XRCC4 rs6869366 polymorphism was analyzed using PCR-RFLP assay. Results: The frequency of XRCC4 rs6869366 GG genotype was more common in the ND and Sch+ND group than controls (p = 0.001 and p = 0.001, respectively). XRCC4 rs6869366 TT genotype was lower in both ND and Sch+ND group compared to controls (p = 0.001 and p = 0.001, respectively). Also, XRCC4 rs6869366 G allele was higher in Sch+ND group than controls (p = 0.001) while XRCC4 rs6869366 T allele was lower in ND group than healthy controls (p=0.001). XRCC4 rs6869366 GT genotype was lower in ND group than control group (p = 0.003). Discussion: These results suggested that the XRCC4 rs6869366 polymorphism G related genotype/allele was associated with susceptibility to both ND and Sch+ND in a Turkish population

Effect of monoamine oxidase B A644G variant on nicotine dependence and/or schizophrenia risk

Objectives: Schizophrenia (Sch) is a severe and chronic mental illness. Smoking prevalence is higher in patients with Sch than general population. We aimed to investigate the effects of MAOB gene A644G variant on nicotine dependence (ND) and Sch+ND risk in Turkish population and to evaluate by bioinformatic analysis. Methods: Present study included 161 individuals with ND, 223 patients with Sch+ND, and 96 non-smoker controls. MAOB A644G variant was analyzed using PCR-RFLP method. As the MAOB gene is located on the X chromosome, each gender was analysed separately. Results: The total distributions of AA, AG and GG genotypes of MAOB gene A644G were 44.7%, 22.4% and 32.9% in the ND group, 45.3%, 25.1% and 29.6% in the Sch+ND group and, 44.8, 22.9% and 32.3% in non-smoker controls. No significant differences were observed between groups for the MAOB A644G genotype and allele frequencies when female group compared to male group (p > 0.05). Examination of disease associations of SNPs from each miRNA gene region in GWAS databases yielded results for aging, bipolar disorder, autoimmune, and neurological diseases. Discussion: Our results indicate that the MAOB gene A644G variant is not associated with ND and/or Sch susceptibility in the Turkish population

Cytokine gene polymorphism frequencies in Turkish population living in Marmara region

Objectives Sequence variants in cytokine genes are related to affect cytokine gene levels. In this study, it was aimed to examine eight single nucleotide polymorphisms (SNPs) in five cytokine genes (TNF-alpha, INF-gamma, IL-6, IL10, TGF-beta) for the Turkish population living in Marmara region and to reveal the genetic distance between the study group and other populations. Methods In this study, three-hundred unrelated healthy individuals were involved and all genotyping were performed by using sequence-specific primers PCR (PCR-SSP) method. The SNP data were analyzed for Hardy Weinberg equilibrium fit by calculating expected genotype frequencies and comparing them to the observed values using Arlequin software version 3.1. The genetic distances between the study group and other populations were calculated and a neighbor-joining tree was constructed by PHYLIP. Results The observed genotypes of TNF-alpha (-308), IFN-gamma (+874), TGF-beta (codon 10), and TGF-beta (codon 25) of the subjects were found to be similar with other populations investigated in this study. However, there is a significant frequency difference for IL-6 and IL-10 genotypes between populations. Conclusions The current population study provided more reference values for these polymorphisms and generated a control group to be used in further association studies especially for transplantation, GVHD, autoimmune and malign disease