Browsing by Author "Doğu, Okan"
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Publication Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease(Elsevier, 2020-09-28) Eryılmaz, Işıl Ezgi; Erer, Sevda; Zarifoğlu, Mehmet; Egeli, Ünal; Karakuş, Ece; Yurdacan, Beste; Çeçener, Gülşah; Tunca, Berrin; Çolakoğlu, Beril; Tokcaer, Ayşe Bora; Saka, Esen; Demirkıran, Meltem; Akbostancı, Cenk; Doğu, Okan; Kaleağası, Hakan; Kenangil, Gülay; Çakmur, Raif; Elibol, Bülent; ERYILMAZ, IŞIL EZGİ; ERER ÖZBEK, ÇİĞDEM SEVDA; ZARİFOĞLU, MEHMET; EGELİ, ÜNAL; Karakuş, Ece; Yurdacan, Beste; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0002-3316-316X; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; GWV-3548-2022; DVY-9744-2022; EHN-5825-2022; AAH-1420-2021; FDA-2023-2022; AEA-0144-2022; AAP-9988-2020; ABI-6078-2020In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele "A" for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele "A" for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group "female"; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.Item Epigenetic approach to early-onset Parkinson's disease: Low methylation status of SNCA and PARK2 promoter regions(Taylor & Francis, 2017-08-12) Elibol, Bülent; Bora, Ayşe Tokcaer; Saka, Esen; Demirkıran, Meltem; Akbostancı, Cenk; Doğu, Okan; Çolakoğlu, Beril; Kenangil, Gülay; Kaleagası, Hakan; Eryılmaz, Işıl Ezgi; Çeçener, Gulşah; Erer, Sevda; Egeli, Ünal; Tunca, Berrin; Zarifoğlu, Mehmet; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; 0000-0002-3316-316X; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; GWV-3548-2022; AAP-9988-2020; AAH-1420-2021; ABI-6078-2020; 57189380840; 6508156530; 25635370800; 55665145000; 6603411305; 6602965754Background and aim: The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD). Materials and methods: The promoter region methylation status of SNCA and PARK2 genes was evaluated by methylation specific-PCR (MSP) in 91 patients with EOPD and 52 healthy individuals. Results: The methylation of SNCA and PARK2 promoter regions were significantly lower in EOPD patients compared to the control group (P = 0.013 and P = 0.03, respectively). We also found that the methylation status of the SNCA might be associated with positive family history of PD (P = 0.042). Conclusion: Although it should be supported by further analysis, based on the results of the present study, the methylation status of SNCA and PARK2 genes might contribute to EOPD pathogenesis.Item Mutation analysis of the PARKIN, PINK1, DJ1, and SNCA genes in Turkish early-onset Parkinson's patients and genotype-phenotype correlations(Elsevier, 2016-09) Kenangil, Gülay; Kaleağası, Hakan; Doğu, Okan; Saka, Esen; Elibol, Bülent; Erer, Sevda; Egeli, Ünal; Zarifoğlu, Mehmet; Tezcan, Gülçin; Çeçener, Gülşah; Tunca, Berrin; Ak, Seçil; Demirdoğen, Elif; Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-5956-8755; AAH-3843-2020; AAP-9988-2020; ABI-6078-2020; F-8554-2017; AAH-1420-2021; 25635370800; 55665145000; 6603411305; 25650627600; 6508156530; 6602965754; 55253485700; 25644460900Objective: Variations in PARK genes (PRKN, PINK1, DJ-1, and SNCA) cause early-onset Parkinson's disease (EOPD) in different populations. In the current study, we aimed to evaluate the frequencies of variations in PARK genes and the effects of these variations on the phenotypes of Turkish EOPD patients. Methods: All coding regions and exon-intron boundaries of the PRKN, PINK1, DJ-1, and SNCA genes were screened by heteroduplex analysis followed by direct sequencing of the detected variants in 50 Turkish EOPD patients. These variants were evaluated using SIFT, PolyPhen, HSF, and LOVD web-based programs. Results: The frequency of EOPD-associated variations in the PRKN gene was 34%. Among these variations, p.A82E in exon 3 and p.Q409X in exon 11 was determined to be pathogenic. We also defined previously unknown cryptic variations, including c.872-35 G > A and c.872-28T > Gin exon 8 of PRKN and c.252 + 30 T > G and c.322 + 4 A > G in exons 4 and 5 of DJ1, respectively, that were associated with EOPD. Although no significant association was observed between the PARK gene mutations and clinical features (P > 0.05), the alterations were related to the clinical symptoms in each patient. Conclusion: An increasing number of studies report that PRKN, PINK), DJ1 and SNCA mutations are associated with early-onset Parkinson's disease; however, a limited number of studies have been conducted in Turkey. Additionally, our study is the first to evaluate the frequency of SNCA mutations in a Turkish population. The aim of this study was determine the frequency distributions of the PRKN, PINK1, DJ1, and SNCA gene mutations and to analyze the relationships between these genetic variations and the clinical phenotype of EOPD in Turkish patients.Publication The role of the dopamine β-hydroxylase functional polymorphism in patients with early-onset parkinson's disease in the Turkish population(Turkish Neurological Soc, 2021-03-01) Erer, Sevda; Eryılmaz, Işıl Ezgi; Çolak, Dilara Kamer; Egeli, Ünal; Çeçener, Gülşah; Tunca, Berrin; Karakuş, Ece; Çolakoğlu, Beril; Tokçaer, Ayşe Bora; Saka, Esen; Demirkıran, Meltem; Akbostancı, Cenk; Zarifoğlu, Mehmet; Doğu, Okan; Kaleagasi, Hakan; Kenangil, Gülay; Çakmur, Raif; Elibol, Bülent; ERER ÖZBEK, ÇİĞDEM SEVDA; ERYILMAZ, IŞIL EZGİ; Çolak, Dilara Kamer; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Karakuş, Ece; ZARİFOĞLU, MEHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0001-7904-883X; 0000-0002-3316-316X; 0000-0002-2274-3230; 0000-0003-4968-2826; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0003-2982-0961; GWV-3548-2022; AAH-1420-2021; DVY-9744-2022; JIP-4494-2023; AAP-9988-2020; ABI-6078-2020; FDA-2023-2022; EHN-5825-2022Objective: A functional single nucleotide polymorphism, rs1611115, in the dopamine beta-hydroxylase (DBH) gene, is reported to regulate plasma enzyme activity levels. Mere, we report the first evaluation of this association in patients with early-onset Parkinson's disease (EOPD) and healthy controls in the Turkish population.Materials and Methods: We evaluated the DBH rs1611115 polymorphism in 114 (64 male and 50 female) Turkish patients with EOPD and 58 sex- and age-matched healthy controls from the Turkish population. A total of 27.2% (n=31) of our patients who had any variation including pathogenic or non-pathogenic missense, non-sense and/or intronic variation with unknown significance in EOPD genes were grouped as "variation-positive EOPD". A total of 50.8% (n=58) of our patients were grouped as "variation and family history-negative EOPD" and the possible contribution of the DBH rs1611115 polymorphism to EOPD pathogenesis was evaluated in this group.Results: There was no significant difference in the genotypic and allelic frequencies of DBH rs1611115 between patients with EOPD and controls. To our knowledge, this is the first evaluation of the DBH rs1611115 polymorphism in patients with EOPD and ethnically matched controls in the Turkish population.Conclusion: Some previous studies have reported conflicting association results between DBH rs1611115 polymorphism and PD pathogenesis in different ethnic groups. Therefore, further studies are needed to evaluate dopamine metabolism-related generic variants and to determine their possible roles in EOPD susceptibility in the Turkish population.