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Association of Myeloperoxidase Gene Functional Variant with Schizophrenia and Smoking in a Turkish Population
(2020) Pehlivan, Sacide; Çetinay, Pınar; Uysal, M. Atilla; Nursal, Ayşe Feyda; Kurnaz, Selin; Sever, Ulgen; Pehlivan, Mustafa
Objective: Etiopathogenesis of schizophrenia (SCZ) involves several risk genes that induce inflammation, environmental stress factors and changes in the innate immune system. Patients with SCZ have the highest rate of cigarette smoking and severe nicotine dependence. Myeloperoxidase (MPO), a member of subfamily of peroxidases, is most abundantly expressed in immune cells. The aim of this study was to investigate the relationship between the MPO rs2333227 variant and SCZ/smoking etiopathogenesis. Method: The study included 54 patients with SCZ, 94 smokers and 92 healthy controls. MPO rs2333227 variant was genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated using the ?2 test. Results: G/G and G/A genotypes of MPO rs2333227 were detected in our study samples. The frequencies of the G/G and G/A genotypes were 53.7%, 46.3%; 56.3%; 43.7%; 68.9%, 31.1% in SCZ patients, smokers, and the control group, respectively. The allele frequencies were G: 76.9% (SCZ patients), 77.4% (smokers) 83.7% (controls); A: 23.1% (SCZ patients), 22.6% (smokers), and 16.3% (controls). There was no significant difference between the SCZ patients, smokers and controls regarding MPO rs2333227 variant either in terms of allele frequency or genotype frequency. Then we genotyped the groups as women and men. MPO rs2333227 variant genotype distribution did not differ between men and women (p>0.05). Conclusion: This study does not support the role of MPO rs2333227 variant in increasing genetic risk for SCZ/smoking in Turkish population.
Association of the TNF-?, IL-2, and IL-2RB gene variants with susceptibility to psoriasis in a Turkish cohort
(Termedia Publishing House Ltd., 2018) Gülel, Aslıhan; İnaloz, Hüseyin Serhat; Nursal, Ayşe Feyda; Sever, Tuğçe; Pehlivan, Sacide
Aim of the study: The aim of this study was to investigate the role TNF-?, IL -2, and IL -2RB variants in psoriasis (Ps) and to evaluate the association between these variants and clinical features. Material and methods: A total of 74 psoriatic patients and 74 healthy individuals were genotyped for these variants by PCR and/or RFLP. Results: The AA genotype of TNF-? (-308) was significantly more common in the patients (p = 0.013). TNF-? (-238) AA genotype was significantly increased in the patients (p = 0.028), while the GG genotype was decreased in the patient group, compared to the controls (p = 0.016). IL-2 (-330) variant GG and TT genotype was more common in the patients (p = 0.037, p = 0.009, respectively), while IL-2 (-330) GT genotype was increased in the control subjects (p = 0.001). IL-2 (-330) GG genotype frequency was significantly decreased (p = 0.021) and the TT genotype frequency was significantly increased among patients with psoriatic arthritis in comparison with Ps patients (p = 0.014). IL-2RB TC genotype frequency was significantly decreased and TT genotype frequency was significantly increased in the patients with positive family history of Ps compared to those who had a negative family history (p = 0.017, p = 0.014, respectively). Also, IL-2RB CC genotype was significantly increased among the patients with late-onset Ps in comparison with the early onset Ps group (p = 0.009). The frequency of IL-2 (-330) TT genotype was significantly higher in mild Ps patients than moderate-severe patients (p = 0.043). Conclusions: Our data suggest a potential role of these genes as candidate genes for susceptibility to Ps in a Turkish cohort.
Association of XRCC1 and XPD functional gene variants with nicotine dependence and/or schizophrenia: a case-control study and in silico analysis
(Taylor and Francis Ltd., 2019) Pehlivan, Sacide; Aydın, Nizamettin; Nursal, Ayşe Feyda; Uysal, Mehmet Atilla; Pehlivan, Mustafa; Tekcan, Akın; Yavuz, Fatih Kasım; Sever, Ülgen; Yavuzlar, Hazal; Kurnaz, Selin; Uysal, Seda; Çetinay Aydın, Pınar
OBJECTIVE: The role of DNA repair mechanisms has received attention recently in schizophrenia (Sch). Sch patients show an increased prevalence of nicotine dependence (ND). This study aimed to find out whether functional SNP variants in the XRCC1 and the XPD play any role both in ND and Sch + ND etiopathogenesis in a Turkish population which was followed up with an in silico analysis approach. METHODS:XRCC1 rs25487 and XPD rs13181 variants were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In the prediction of pathogenic effect of rs25487 and rs13181 SNPs, the PANTHER and SNPs&GO programs were used. Also, the protein–protein interaction analysis was performed to retrieve functional partners of the XRCC1 and XPD protein. RESULTS:XRRC1 rs25487 GG genotype was significantly lower in both ND and Sch + ND groups than the controls (p =.001, p =.006) while G allele was lower only in Sch + ND group comparison to controls (p =.034). XPD rs13181 Lys/Lys genotype was more lower in both Sch + ND and ND groups than in controls (p =.007; p =.001). XPD rs13181 Gln allele was lower in Sch + ND group compared to controls while Lys allele was higher in ND group than controls, respectively (p =.034; p =.008). The results of in silico prediction analysis showed that the rs25487 had neutral effect while the rs13181 had a disease-related effect. CONCLUSIONS: The results of the current study revealed a possible genetic association between XRCC1/XPD variants and both in ND and Sch + ND. We think that analysis of this missense SNPs using bioinformatics methods would help diagnosis of XRCC1 and XPD-related diseases. © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
CNR2 rs2229579 and COMT Val158Met variants, but not CNR2 rs2501432, IL-17 rs763780 and UCP2 rs659366, contribute to susceptibility to substance use disorder in the Turkish population
(Taylor & Francis Ltd, 2019) Kurnaz, Selin; Yazici, Ahmet Bulent; Nursal, Ayse Feyda; Aydin, Pinar Cetinay; Atar, Ayca Ongel; Aydin, Nazan; Pehlivan, Sacide
OBJECTIVE: Substance use disorders (SUD) are among the most important public health problems throughout the world. We investigated whether COMT (Val108/158Met), CNR2 (rs2501432 and rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants were associated with SUD and its clinical parameters in a Turkish population. METHODS: We conducted a case-control study among 136 subjects with SUD and 100 healthy controls. Six variants were analysed by the PCR-RFLP method. RESULTS: The CNR2 rs2229579 T/T genotype and T allele increased in SUD groups than controls while the C/C genotype and C allele were more prevalent in the control group compared to the SUD group (p = 0.000 and p = 0.001, respectively). The COMT Val108/158Met Val/Val genotype and Val allele were significantly associated with polysubstance abuse (p < 0.05). There was no significant difference between the SUD group and control group regarding genotype and allele frequencies of COMT (Val108/158Met), CNR2 (rs2501432), UCP2 (rs659366) and IL-17 (rs763780) variants. CONCLUSIONS: This is the first study that discussed the relation of these variants and SUD patients in the Turkish population. The results of the analysis indicated that the CNR2 rs2229579 variant has an effect on susceptibility to SUD, suggesting that this variant might play a role in the physiopathology of SUD. The COMT Val108/158Met variant might be an important factor affecting polysubstance use.
CYP2A6 gene variants may explain smoking status in a Turkish cohort
(Taylor and Francis Ltd., 2018) Pehlivan, Sacide; Uysal, Mehmet Atilla; Çağatay, Tülin; Nursal, Ayşe Feyda; Kekik Çınar, Çiğdem; Erkan, Feyza; Sever, Ülgen; Bingöl, Züleyha; Pehlivan, Mustafa; Pençe, Sadrettin
OBJECTIVE: Nicotine is the main addictive agent present in tobacco and is principally metabolized by a cytochrome P450-mediated oxidation process. While smoking patterns differ widely among smokers, the metabolization rate of nicotine can also be affected by variations in rates of enzyme activity between individuals. Therefore, we aimed to investigate the significance of CYP2A gene variants in the smoking status in a Turkish population using next-generation sequencing (NGS). METHODS: This case–control study involved 64 subjects with Nicotine dependence (ND) and 36 Non-smoker (NS) subjects. Amplicants designed by “Primer-BLAST” programme were all sequenced using the “Illimuna-MiseqQ-platform”. RESULTS: It was found that there were five SNPs in the CYP2A6 gene (rs8192725, rs7248240, rs1809810, rs8192733 and rs28399435). CYP2A6 rs1809810 homozygous TT genotype and T allele were seen in lower percentages in ND group compared to the NS group (p =0.045; p =0.021). Individuals with CYP2A6 rs1809810 TT genotypes and T allele showed odds ratio of 4.760 and 5.360 for developing protective role ND, respectively. CYP2A6 rs8192733 CC genotype and C allele were both lower in ND group (respectively p =0.001, p =0.023) while GC genotype was higher in the ND group (p =0.004). CYP2A6 rs28399435 TT genotype and T allele were more common in the ND group (respectively p =0.001, p =0.001). CYP2A6 rs28399435 CC genotype was lower in the ND group than in the NS group (p =0.010). CONCLUSIONS:CYP2A6 rs1809810, rs8192733, rs28399435 could be genetic risk factors for ND in a Turkish population. © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Cytokine gene variants/expressions and non-syndromic microtia – Is there a link?
(Continuing Education, and Scientific Research Association (CESRA), 2017) Nursal, Ayşe Feyda; Bekerecioğlu, Mehmet; Pehlivan, Sacide; Sever, Tuğçe; Büyükgüral, Berker
Sitokin gen varyantları/ekspresyonları ve non-sendromik mikrotia - Bir ilişki var mıdır?Amaç: Mikrotianın etyopatogenezinde birçok genetik ve çevreselfaktörler araştırılmasına rağmen hala belirsizlik vardır. Bu çalışmadabir Türk kohortunda pro- ve anti-enflamatuar sitokinlerin [interlökin(IL) 6, IL-10, tümör nekroz faktör alfa (TNF-?), transforme edici büyüme faktörü beta (TGF-?1), İnterferon gama (IFN-?)] varyant/ekspresyonu ve sendromik-olmayan mikrotiaya yatkınlık arasındaki ilişkiyi araştırdık.Yöntem:Çalışmaya akraba olmayan 19 mikrotiyalı olgu ve 40 sağlıklı gönüllü kontrol dahil edildi. Sitokin varyantları dizi spesifik primerpolimeraz zincir reaksiyonu (PCR-SSP) metodu kullanılarak analizedildi. Bulgular:IL-6 (-174) GC genotipi (yüksek ekspresyon) mikrotia vakalarında daha düşükken (p=0.003), IL-6 (-174) GG genotipi (yüksekekspresyon) mikrotia vakalarında kontrolden daha yüksek olarak bulundu (p=0.010). IL-6 (-174) için, GG genotipi taşıyan hastalar mikrotia için 5895 kat yüksek riske sahipti. IFN-? (+874) varyant AA genotip (düşük ekspresyon) mikrotia vakalarında düşüktü (p=0.009). IL6 (-174) C alleli hastalarda kontrollere göre düşükken, G alleli hastagrubunda kontrole göre daha yaygındı (p=0.003). IFN-? (+874) varyant A alleli hastalarda düşükken, T alleli hastalarda daha yaygındı(p=0.017). Sonuç:Burada mikrotia gelişimi için sitokin varyantlarının risk faktörü teşkil edeceğini ilk defa gösterdik. Sonuçlarımız IFN-?(+874) veIL-6 (-174) varyantlarının Türk toplumunda mikrotia gelişimi ile ilişkili olabileceğini öne sürmektedir.
Do UCP2, IL-17, mi196a2, and NR3C1 gene variants contribute to the risk of microtia? A preliminary study in Turkish population
(Elsevier Science Bv, 2018) Ozdilli, Kursat; Bekerecioglu, Mehmet; Nursal, Ayse Feyda; Pehlivan, Mustafa; Sever, Ulgen; Buyukgural, Berker; Pehlivan, Sacide
[Abstract Not Available]
Dopamine D4 Receptor Gene Exon III VNTR Variant influences smoking status in Turkish population
(Turkish Neuropsychiatric Society, 2019) Uysal, Mehmet Atilla; Sever, Ülgen; Nursal, Ayşe Feyda; Yedikule Smoking Cessation Study Group; Pehlivan, Sacide
Introduction: Dopaminergic gene variants may affect nicotine dependence through their possible impact on the dopamine reward pathway. The purpose of this study is to investigate the relationship between the variable number tandem repeat (VNTR) variant in exon III of the Dopamine D4 receptor (DRD4) gene and genetic predisposition of smoking status in a Turkish population. Methods: We performed a study comparing 154 subjects as the smoker group, and 111 subjects as the non-smoker group. Genotyping for the DRD4 VNTR variant was performed using a PCR method. Results: There was a significant difference between smoker and nonsmoker groups regarding the distribution of the alleles and genotypes of the DRD4 gene (p=0.000, p=0.000, respectively). The 2R allele was higher in the non-smoker group compare to the smoker group (p=0.000). We found that the 2/7 and 4/9 genotypes were more common in smokers than non-smoker group (p=0.037, p=0.028, respectively) while 2/4 genotype was more prevalent in non-smokers than smokers (p=0.000). When the number of repeat alleles (48 bp) are accepted as short (S) if six or less, and as long (L) if seven or more, it was found that the frequency of S/S genotype of the DRD4 VNTR variant was lower in the smoker group and S/L genotype was higher in the smoker group (p=0.006, p=0.006, respectively). The subjects carrying the S/L genotype have a 2.25-fold increased risk for smoking than a non-smoker. Conclusion: The results indicated that the subjects carrying DRD4 exon III VNTR S/L genotype have a risk for smoking status in a Turkish population.
Dopamine D4 Receptor Gene Exon III VNTR Variant Influences Smoking Status in Turkish Population
(2019) Uysal, Mehmet Atilla; Sever, Ülgen; Nursal, Ayşe Feyda; Group, Yedikule Smoking Cessation Study; Pehlivan, Sacide
Introduction: Dopaminergic gene variants may affect nicotine dependence through their possible impact on the dopamine reward pathway. The purpose of this study is to investigate the relationship between the variable number tandem repeat (VNTR) variant in exon III of the Dopamine D4 receptor (DRD4) gene and genetic predisposition of smoking status in a Turkish population. Methods: We performed a study comparing 154 subjects as the smoker group, and 111 subjects as the non-smoker group. Genotyping for the DRD4 VNTR variant was performed using a PCR method. Results: There was a significant difference between smoker and nonsmoker groups regarding the distribution of the alleles and genotypes of the DRD4 gene (p=0.000, p=0.000, respectively). The 2R allele was higher in the non-smoker group compare to the smoker group (p=0.000). We found that the 2/7 and 4/9 genotypes were more common in smokers than non-smoker group (p=0.037, p=0.028, respectively) while 2/4 genotype was more prevalent in non-smokers than smokers (p=0.000). When the number of repeat alleles (48 bp) are accepted as short (S) if six or less, and as long (L) if seven or more, it was found that the frequency of S/S genotype of the DRD4 VNTR variant was lower in the smoker group and S/L genotype was higher in the smoker group (p=0.006, p=0.006, respectively). The subjects carrying the S/L genotype have a 2.25-fold increased risk for smoking than a non-smoker. Conclusion: The results indicated that the subjects carrying DRD4 exon III VNTR S/L genotype have a risk for smoking status in a Turkish population.
Effect of monoamine oxidase B A644G variant on nicotine dependence and/or schizophrenia risk
(Universidade de Sao Paulo, 2019) Pehlivan, Sacide; Çetinay Aydın, Pınar; Uysal, Mehmet Atilla; Şentürk Çiftçi, Hayriye; Sever, Ülgen; Yavuz, Fatih Kasım; Aydın, Nazan; Nursal, Ayşe Feyda
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. © 2019, Universidade de Sao Paulo. All rights reserved.
Effect of the IL-17F rs763780 Variant on Chronic Lymphocytic Leukemia and Multiple Myeloma Risk in a Turkish Cohort
(2018) Nursal, Ayşe Feyda; Pehlivan, Mustafa; Kurnaz, Selin; Pehlivan, Sacide
Introduction: Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in developed countries. Multiple myeloma (MM), a clonal plasma cell disease, is the second most prevalent hematological cancer. Interleukin-17 (IL-17) can facilitate the secretion of numerous proinflammatory cytokines. The goal of the present study was to evalu-ate the effect of IL-17F rs763780 on CLL/MM susceptibility in a Turkish cohort. Methods: The study included 37 patients with CLL, 21 patients with MM, and 100 healthy controls. The IL-17F rs763780 variant was genoty-ped using polymerase chain reaction-restriction fragment length poly-morphism (PCR-RFLP). The frequencies of the alleles and genotypes in patient and control groups were compared by the ?2 test. Results: No significant difference was found in the distribution of ge-notypes and alleles frequencies for IL-17F rs 763780 between the pati-ents and the healthy controls (P>0.05).Conclusion: Our results suggest that IL-17 rs763780 variant may not contribute to CLL and MM pathogenesis.
Endotelyal nitrik oksit sentaz (eNOS) ve miyeloperoksidaz (MPO) genlerin mikrotiyadaki rolü
(2016) Büyükgüral, Berker; Pehlivan, Sacide; Nursal, Ayşe Feyda; Bekerecioğlu, Mehmet
Amaç: Bu çalışmanın amacı endotelyal nitrik oksit sentaz (eNOS) polimorfizmleriyle miyeloperoksidaz (MPO) genleri ve mikrotiya gelişimi arasındaki ilişkiyi belirlemekti. Yöntem:Çalışmaya akraba olmayan 19 (11 erkek, 8 kadın) mikrotiyalıolgu ve 40 sağlıklı kontrol alındı. Çalışma, ekson 7'nin bir varyantı(G894T), eNOS geninin 4. nitronunda (VNTR) değişken sayıda 27 bpardışık tekrarlar ve MPO geninin promoter bölgesinde (G463A) bir varyant olmak üzere üç fonksiyonel varyant üzerine odaklandı. Polimerazzincir reaksiyonu (PCR) ve/veya PCR-restriksiyon parça uzunluk polimorfizm (RFLP) yöntemi kullanarak bu varyantların genotiplerini çıkardık. Ki-kare testi kullanarak mikrotiya olgularıyla sağlıklı kontroller arasında eNOS ve MPO genlerinde alel ve genotip dağılımını karşılaştırdık. Bulgular:eNOS (G894T) varyantı açısından, mikrotiya olgularıyla sağlıklı kontroller arasında genotip dağılımı açısından önemli bir farklılıkvardı (OR: 1.267, %95 GA: 1.004-1.598; p=0.009). Çalışmamız eNOS(G894T) TT genotipli olgularda mikrotiya riskinin arttığını gösterdi.eNOS (VNTR) varyanının alel sıklıkları mikrotiya olgularıyla sağlıklıkontroller arasında istatistiksel açıdan anlamlı farklılık olduğunu gösterdi(OR: 2.947, %95 GA: 1.188-7.311; p=0.028). Olgularda eNOS (VNTR)B aleli daha yüksek sıklıkta görülmüştür. Ancak genotip dağılımına göreMPO (G463A) varyantı, genotip dağılımı ve alel sıklığı açısından mikrotiya olguları ve sağlıklı kontroller arasında anlamlı bir farklılık yoktu.Sonuç:Bildiğimiz kadarıyla bu çalışma ile mikrotiya olgularındaeNOS (G894T ve VNTR) ve MPO (G463A) varyantları ilk kez incelenmiştir. Verilerimiz eNOS gen varyantları Türk halkındaki mikrotiyanın etyopatogenezinde kritik rol oynayabildiğini göstermektedir.Güncel çalışmanın bulguları genetik yatkınlık ve dışsal etmenlerin etkileşimde olduğu bir multifaktöryel etiyolojili hastalıkta değişik faktörlerin göreceli katkılarını aydınlatmada prospektif uzunlamasına çalışmaların gerekliliğini vurgulamaktadır.
eNOS and XRCC4 VNTR variants contribute to formation of nicotine dependence and/or schizophrenia
(Comenius University, 2017) Pehlivan, Sacide; Uysal, Mehmet Ali; Aydın, Pelin C.; Pehlivan, Mustafa; Nursal, Ayşe Feyda; Yavuzlar, Hazal; Kurnaz, Serdar; Sever, Ülgen; Yavuz, Ferhat K.; Uysal, Sezer; Aydın, Nazan
BACKGROUND: This study aimed to evaluate whether VNTR variants in the Endothelial Nitric Oxide Synthase (eNOS) and the XRCC4 gene play any role in nicotine dependence (ND) and/or Schizophrenia+ND (Sch+ND) ethiopathogenesis. METHODS: Present study included 100 individuals with ND, 60 patients with Sch+ND, and 70 healthy controls. These variants were analyzed using PCR. RESULTS: The cases with ND had higher eNOS VNTR-BB genotype than the healthy control subjects (p = 0.001). eNOS-AA genotype was lower in cases with Sch+ND and ND groups compared to the controls (p = 0.001, p = 0.001, respectively). eNOS-B allele was found significantly more frequently in Sch+ND group compared to the controls (p = 0.001). eNOS-A allele was significantly lower in ND group than the controls (p = 0.001). XRCC4-ID genotype was more common in the ND group than the control group (p = 0.001) as heterozygosity disadvantage. XRCC4-DD genotype was more common in the Sch+ND group compared to the controls (p = 0.035). The frequency of XRCC4-I allele was lower in the Sch+ND group compared to the controls (p = 0.012). CONCLUSIONS: Our results showed that eNOS and XRCC4 VNTR variants might play a potential role in Sch+ND and/or ND pathophysiology.
Global and glucocorticoid receptor gene-specific (NR3C1) DNA methylation analysis in patients with cannabinoid or synthetic cannabinoid use disorder
(Elsevier Ireland Ltd, 2021) Pehlivan, Sacide; Aytac, Hasan Mervan; Aydin, Pinar Cetinay; Nursal, Ayse Feyda; Pehlivan, Mustafa
This study investigates the relationship between cannabinoid use disorder (CUD) or synthetic cannabinoid use disorder (SCUD) and the global methylation, methylation of NR3C1 gene promotor, and NR3C1 BclI poly-morphism, considering clinical parameters. Based on the DSM-5 criteria, 172 SCUD patients? and 44 CUD pa-tients? diagnoses were confirmed with a positive urine test; 88 healthy volunteers were also included in the study. Global DNA methylation was measured using a 5-methylcytosine (5-mC) DNA ELISA Kit. Methylation-specific PCR was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR-RFLP. Our results demonstrated that the mean of 5-mC percentages of SCUD patients differed significantly from those of the control group. When comparing NR3C1 gene methyl-ation and clinical parameters due to NR3C1 genotype distribution in patients, the genotype distribution was significantly different between the groups, due to the former polysubstance abuse. Additionally, there was a significantly positive correlation between the 5-mC percentages of SCUD patients and the reported durations of their disorders. In summary, whereas global DNA methylation may be associated with SCUD, the methylation of the NR3C1 gene and NR3C1 BclI polymorphism were not related to CUD or SCUD.
Impact of UCP2 -866G/A Variant on Smoking Risk
(2021) Nursal, Ayşe Feyda; Uysal, M. Atilla; Pehlivan, Mustafa; Sever, Ulgen; Pehlivan, Sacide
Objective: Mitochondria are multifunctional and dynamic organelles found in cells. Nicotine is a natural alkaloid found in the tobacco plant and has been well studied as a component of cigarette smoke. It has also been reported to affect mitochondrial function both in vitro and in vivo. Uncoupling protein 2 (UCP2) reduces generation of ROS by mitochondria. Our purpose in this study was to investigate whether the -866G/A variant of the UCP2 gene is associated with smoking status. Methods: A total of 238 individuals consisting of 138 smokers and 100 healthy controls were examined. The UCP2-866G/A variant was genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Results: The proportion of individuals carrying the three possible genotype was significantly different between the smoker and healthy control groups. The UCP2-866G/A variant GG genotype was associated significantly with an increased risk of smoking (p=0.001) while AA genotype was associated significantly with a decreased risk of smoking (p=0.001). The UCP2-866G/A variant G allele was found to be increased in the smoker group compared to the healthy controls (p=0.001). Conclusion: Our data suggest that the UCP2-866 G/A variant GG genotype and G allele might reflect the risk of smoking status in a Turkish population
Interleukin-1 gene variants and the risk of non-syndromic microtia
(Pamukkale Üniversitesi, 2018) Nursal, Ayşe Feyda; Bekerecioğlu, Mehmet; Büyükgüral, Berker; Pehlivan, Sacide
Purpose: Microtia is a congenital anomaly, manifested by a small and disfigured auricle. Interleukin (IL) 1 is an important mediator of inflammation and cartilage destruction, This study is aimed at investigating association of IL-1A (-889) and IL-1B (-511) variants in a Turkish patient population with microtia. Meterials and Methods: Nineteen patients diagnosed with microtia and 40 healthy controls were enrolled to the study. The IL-1A (-889) and IL-1B (-511) variants were evaluated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. For statistical analysis, SPSS version 22.0 was used. Results: The genotype distribution of the IL-1A (-889) variant was statistically different between the cases and the control group. IL-1A -889 CC genotype was lower in microtia cases while TT genotype was more prevalent in microtia cases, respectively (p=0.008, p=0.008). High difference was also observed when the patient group and the control group were compared according to IL-1 (-889) CT+TT (p=0.003). IL-1A (-889) C allele was lower in microtia patients and T allele was higher in patients (p=0.005). The allele frequency and genotype distribution of IL-1B (-511) CT variant did not show any statistically difference between patients and controls (p>0.05). Conclusion: To our knowledge, for the first time in the literature we have demonstrated a significant association of the IL-1A (-889) functional variant with microtia in a Turkish cohort.
Investigating the eNOS and IFN-gamma Gene Variants Susceptible to Bipolar Disorder or Schizophrenia in a Turkish Cohort
(Turkish Assoc Psychopharmacology, 2020) Pehlivan, Sacide; Aytac, Hasan Mervan; Ciftci, Hayriye Senturk; Oyaci, Yasemin; Pehlivan, Mustafa; Nursal, Ayse Feyda
Background: Schizophrenia (Sch) and bipolar disorder (BD) are debilitating chronic psychiatric disorders that are both etiologically and clinically heterogeneous. According to the gathered evidence, multiple mental disorders are accompanied by inflammation. Interferon-gamma (IFN-gamma), as a regulatory cytokine, is involved in the immune response as a proinflammatory mediator. Several critical physiological functions are regulated and governed by nitric oxide (NO) in the central nervous system. This study aimed to investigate the association between IFN-gamma +874T/A and eNOS 894G/T variants and Sch or BD susceptibility. Methods: Blood samples were collected from patients and healthy subjects. IFN-gamma +874T/A and eNOS 894G/T variants were genotyped with the PCR-RFLP. We evaluated the patients with some clinical parameters (the duration of the disorder, age of onset, number of hospitalizations, family history, tobacco smoking or drug, alcohol usage). Statistical analyses were performed using the SPSS version. Results: When the genotype distributions and allele frequencies of the IFN-gamma +874T/A and eNOS 894G/T in the patients diagnosed with Sch or BD were compared with the control group, there were not found to be significant differences between the groups. When comparing IFN-gamma +874T/A and eNOS 894G/T genotype distributions and allele frequencies of Sch or BD patients due to clinical parameters, the genotype distribution of IFN-gamma +874T/A in BD patients was significantly different between the groups due to the presence of tobacco smoking (OR: 0.217, 95%Cl: 0.054-0.878; p = 0.032). Conclusions: To the best of our knowledge, this is the first study that examines the association between the IFN-gamma and eNOS gene variants and Sch or BD in a Turkish population. Although IFN-gamma +874T/A and eNOS 894G/T variants are not considered as candidate genes for Sch or BD, the results indicated that the BD patients carrying IFN-gamma +874T/A AA genotype were less susceptible to tobacco smoking in a Turkish population.
Is Complement Factor H Tyr402His Variant a Potential Cause of Ankylosing Spondylitis?
(2020) Pehlivan, Sacide; Akaltun, Mazlum Serdar; Pehlivan, Mustafa; Gürsoy, Savaş; Nursal, Ayşe Feyda
Aim: Ankylosing spondylitis (AS) is an autoimmune disease caused by chronic inflammatory response. Complement system is the major component of the innate immune defence. In this study, we investigated the potential association between complement factor H (CFH) gene Tyr402His variant (rs1061170) with AS in a Turkish population. Methods: Seventy-eight AS patients and 80 healthy individuals were enrolled in the present study as case and control subjects, respectively. The Tyr402His variant of CFH gene was analysed by PCR-RFLP method. Results: There was no statistically significant difference between AS patients and healthy controls in terms of CFH Tyr402His genotype and allele frequencies. However, the visual analogue scale (VAS) daytime and the AS Quality of Life (ASQoL) were significantly different according to CFH Tyr402His genotype distribution (p=0.032 and p=0.036, respectively). VAS of daytime and ASQoL were higher in subjects carrying Tyr402His variant Tyr/Tyr + Tyr/His genotypes compared to those carrying His/His genotype. Conclusion: This is the first study evaluating the association between CFH Tyr402His and susceptibility to AS in a Turkish population. Although CFH Tyr402His variant was not considered a candidate gene for AS susceptibility in our samples, some clinical findings seem to be associated with genotype distribution of CFH Tyr402His variant.
Is there any Association between the Functional Variants of the NOS3 Gene and Psoriasis?
(Aves, 2018) Pehlivan, Sacide; Inaloz, Huseyin Serhat; Nursal, Ayse Feyda; Gulel, Aslihan; Pehlivan, Mustafa
Introduction: Psoriasis (Ps) is a chronic, immune-mediated inflammatory skin disorder with an incompletely understood etiology. The aim of this study was to investigate the relationship between the suspectibility to Ps and G894T (rs1799983) and variable number tandem repeat (VNTR) variants of the endothelial nitric oxide synthase (NOS3) gene. Methods: This is a case-controlled study that included 74 Ps patients in addition to 74 matched healthy unrelated controls from the same locality. The NOS3 gene variants were analyzed by polymerase chain reaction (PCR) and/or PCR-restriction fragment lenght polymorphism (PCR-RFLP). Results: The NOS3 G894T TT genotype and T allele were more common in the Ps group compared to the healthy controls (p=0.000, p=0.001, respectively). The NOS3 VNTR variant BB genotype and B allele were higher in the patient group than in the control group (p=0.005, p=0.000 respectively). The NOS3 VNTR AA genotype was lower in the patient group (p=0.027). However, a stratified analysis including arthritis, the Ps area and severity index (PASI), the age of onset, and family history revealed no significant correlation between the NOS3 G894T and NOS3 VNTR genotypes (p>0.05). Conclusion: These results suggest that the NOS3 G894T and VNTR variants are associated with Ps in a Turkish cohort. However, future studies are needed to understand the genetic role of the NOS3 variants in the development of Ps.
Is there any Association between the Functional Variants of the NOS3 Gene and Psoriasis?
(2018) Pehlivan, Sacide; İnalöz, Hüseyin Serhat; Nursal, Ayşe Feyda; Gülel, Aslıhan; Pehlivan, Mustafa
Introduction: Psoriasis (Ps) is a chronic, immune-mediated inflammatory skin disorder with an incompletely understood etiology. The aim of this study was to investigate the relationship between the suspectibility to Ps and G894T (rs1799983) and variable number tandem repeat (VNTR) variants of the endothelial nitric oxide synthase (NOS3) gene. Methods: This is a case-controlled study that included 74 Ps patients in addition to 74 matched healthy unrelated controls from the same locality. The NOS3 gene variants were analyzed by polymerase chain reaction (PCR) and/or PCR- restriction fragment lenght polymorphism (PCR-RFLP). Results: The NOS3 G894T TT genotype and T allele were more common in the Ps group compared to the healthy controls (p=0.000, p=0.001, respectively). The NOS3 VNTR variant BB genotype and B allele were higher in the patient group than in the control group (p=0.005, p=0.000 respectively). The NOS3 VNTR AA genotype was lower in the patient group (p=0.027). However, a stratified analysis including arthritis, the Ps area and severity index (PASI), the age of onset, and family history revealed no significant correlation between the NOS3 G894T and NOS3 VNTR genotypes (p>0.05). Conclusion: These results suggest that the NOS3 G894T and VNTR variants are associated with Ps in a Turkish cohort. However, future studies are needed to understand the genetic role of the NOS3 variants in the development of Ps.

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