scholarly journals The SNCA-Rep1 Polymorphic Locus: Association with the Risk of Parkinson’s Disease and SNCA Gene Methylation

Acta Naturae ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 105-110 ◽  
Author(s):  
E. V. Iakovenko ◽  
N. Yu. Abramycheva ◽  
E. Yu. Fedotova ◽  
S. N. Illarioshkin
Keyword(s):  
Molecular Marker ◽  
Polymorphic Locus ◽  
Alpha Synuclein ◽  
Gene Methylation ◽  
Allelic Variants ◽  
Parkinsons Disease ◽  
Cpg Sites ◽  
Snca Gene ◽  
Intron 1 ◽  
Significant Region

Neurodegeneration in Parkinsons disease is characterized by the accumulation of alpha-synuclein, aprotein encoded by theSNCAgene, in neurons. In addition to mutations, many polymorphisms have been identified in this gene, and one of theseis a dinucleotide microsatellite:SNCA-Rep1.The mechanisms by which specific configurations ofSNCA-Rep1 may contribute to the development of this disease have yet to be clarified. Inour study, a relationship between longSNCA-Rep1 alleles and Parkinsons was confirmed in the Russian population. Long allelic variants ofSNCA-Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of theSNCAgene. Long variants ofSNCA-Rep1 are supposed to exert their effect through the hypomethylation of atranscriptionally significant region of this gene. Hypomethylation is usually associated with increased expression, which, in turn, contributes to alpha-synuclein accumulation in neuronal cytoplasm, with the latter being the main molecular marker of Parkinsons disease. Further studies are needed to establish a relationship between our finding andSNCAgene expression.

scholarly journals The SNCA-Rep1 Polymorphic Locus: Association with the Risk of Parkinson’s Disease and SNCA Gene Methylation

Acta Naturae ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 105-110
Author(s):  
E. V. Iakovenko ◽  
N. Yu. Abramycheva ◽  
E. Yu. Fedotova ◽  
S. N. Illarioshkin
Keyword(s):  
Molecular Marker ◽  
Polymorphic Locus ◽  
Alpha Synuclein ◽  
Gene Methylation ◽  
Allelic Variants ◽  
Parkinsons Disease ◽  
Cpg Sites ◽  
Snca Gene ◽  
Intron 1 ◽  
Significant Region

Neurodegeneration in Parkinsons disease is characterized by the accumulation of alpha-synuclein, aprotein encoded by theSNCAgene, in neurons. In addition to mutations, many polymorphisms have been identified in this gene, and one of theseis a dinucleotide microsatellite:SNCA-Rep1.The mechanisms by which specific configurations ofSNCA-Rep1 may contribute to the development of this disease have yet to be clarified. Inour study, a relationship between longSNCA-Rep1 alleles and Parkinsons was confirmed in the Russian population. Long allelic variants ofSNCA-Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of theSNCAgene. Long variants ofSNCA-Rep1 are supposed to exert their effect through the hypomethylation of atranscriptionally significant region of this gene. Hypomethylation is usually associated with increased expression, which, in turn, contributes to alpha-synuclein accumulation in neuronal cytoplasm, with the latter being the main molecular marker of Parkinsons disease. Further studies are needed to establish a relationship between our finding andSNCAgene expression.

Epigenetic regulation of SNCA gene expression in Parkinson’s disease

2020 ◽  
pp. 96-98
Author(s):  
А.К. Емельянов ◽  
А.О. Лавринова ◽  
Н.В. Мельникова ◽  
А.А. Дмитриев ◽  
И.В. Милюхина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Cpg Island ◽  
Alpha Synuclein ◽  
Peripheral Blood Cells ◽  
Snca Gene ◽  
Intron 1 ◽  
And Control ◽  
First Time

В настоящем исследовании проведена оценка уровня мРНК и белка генов SNCA, DNMT1, а также степени метилирования интрона 1 гена SNCA в CD45+ клетках периферической крови пациентов со спорадической болезнью Паркинсона (БП) и индивидуумов контрольной группы. Впервые было выявлено снижение концентрации белка DNMT1 в CD45+ клетках периферической крови пациентов с БП по сравнению с группой контроля. Обнаружено увеличение уровня мРНК гена DNMT1 у пациентов с БП по сравнению с контролем. Не выявлено статистически значимых различий при сравнении степени метилирования интрона 1 гена SNCA в CD45+ клетках периферической крови пациентов с БП и контроля. В группе контроля выявлена обратная корреляция степени метилирования отдельных CpG островков с концентрацией белка альфа-синуклеина и уровнем мРНК гена SNCA. Проведенное исследование позволяет предположить участие гена DNMT1 в патогенезе БП и отсутствие ассоциации степени метилирования интрона 1 гена SNCA с БП. The aim of this study was to assess the level of mRNA and protein of the SNCA, DNMT1 genes, as well as intron 1 methylation of the SNCA gene in CD45 + peripheral blood cells of patients with sporadic PD and control individuals. For the first time, a decrease in the concentration of DNMT1 protein in CD45 + peripheral blood cells from PD patients compare to controls was revealed. An increase in DNMT1 gene expression in PD patients compare to controls was found. No differences in intron 1 methylation of the SNCA gene in CD45 + peripheral blood cells was found between PD patients and controls. An inverse correlations between methylation level of 21, 22 CpG island in intron1 of SNCA gene and mRNA SNCA gene and alpha-synuclein protein level were found. The study suggests the involvement of DNMT1 in the pathogenesis of PD and the lack of association of PD with intron 1 methylation of the SNCA gene.

Membrane Interactions of Oligomeric Alpha-Synuclein: Potential Role in Parkinsons Disease

2010 ◽  
Vol 11 (5) ◽  
pp. 334-342 ◽  
Author(s):  
Bart D. van Rooijen ◽  
Mireille M.A.E. Claessens ◽  
Vinod Subramaniam
Keyword(s):  
Potential Role ◽  
Alpha Synuclein ◽  
Membrane Interactions ◽  
Parkinsons Disease

scholarly journals Fragile X Mental Retardation 1 (FMR1) Intron 1 Methylation in Blood Predicts Verbal Cognitive Impairment in Female Carriers of Expanded FMR1 Alleles: Evidence from a Pilot Study

2012 ◽  
Vol 58 (3) ◽  
pp. 590-598 ◽  
Author(s):  
David E Godler ◽  
Howard R Slater ◽  
Quang M Bui ◽  
Elsdon Storey ◽  
Michele Y Ono ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Cognitive Impairment ◽  
Fragile X ◽  
Cognitive Status ◽  
Verbal Iq ◽  
Fragile X Mental Retardation ◽  
Cpg Sites ◽  
Cgg Repeats ◽  
Intron 1 ◽  
Study Participants

Abstract BACKGROUND Cognitive status in females with mutations in the FMR1 (fragile X mental retardation 1) gene is highly variable. A biomarker would be of value for predicting which individuals were liable to develop cognitive impairment and could benefit from early intervention. A detailed analysis of CpG sites bridging exon 1 and intron 1 of FMR1, known as fragile X–related epigenetic element 2 (FREE2), suggests that a simple blood test could identify these individuals. METHODS Study participants included 74 control females (<40 CGG repeats), 62 premutation (PM) females (55–200 CGG repeats), and 18 full-mutation (FM) females assessed with Wechsler intelligence quotient (IQ) tests. We used MALDI-TOF mass spectrometry to determine the methylation status of FREE2 CpG sites that best identified low-functioning (IQ <70) FM females (>200 CGG repeats), compared the results with those for Southern blot FMR1 activation ratios, and related these assessments to the level of production of the FMR1 protein product in blood. RESULTS A methylation analysis of intron 1 CpG sites 10–12 showed the highest diagnostic sensitivity (100%) and specificity (98%) of all the molecular measures tested for detecting females with a standardized verbal IQ of <70 among the study participants. In the group consisting of only FM females, methylation of these sites was significantly correlated with full-scale IQ, verbal IQ, and performance IQ. Several verbal subtest scores showed strong correlation with the methylation of these sites (P = 1.2 × 10−5) after adjustment for multiple measures. CONCLUSIONS The data suggest that hypermethylation of the FMR1 intron 1 sites in blood is predictive of cognitive impairment in FM females, with implications for improved fragile X syndrome diagnostics in young children and screening of the newborn population.

The metabolomics of alpha-synuclein (SNCA) gene deletion and mutation in mouse brain

Metabolomics ◽  
2013 ◽  
Vol 10 (1) ◽  
pp. 114-122 ◽  
Author(s):  
Ruth E. Musgrove ◽  
James Horne ◽  
Richard Wilson ◽  
Anna E. King ◽  
Lindsay M. Edwards ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Gene Deletion ◽  
Alpha Synuclein ◽  
Snca Gene

scholarly journals A COMPLEMENTARY APPROACH ON OLFACTORY DYSFUNCTION IN PARKINSONS DISEASE- RETROSPECTIVE OBSERVATIONAL STUDY

2020 ◽  
pp. 25-32
Author(s):  
Nair Sandeep Damodharan ◽  
Vijayagopal Sunil Kumar ◽  
Przuntek Horst ◽  
Webering Nadine ◽  
Hegelmaier Tobias
Keyword(s):  
Neuronal Degeneration ◽  
Alpha Synuclein ◽  
Olfactory Dysfunction ◽  
Motor Symptom ◽  
Test Results ◽  
Parkinsons Disease ◽  
Complementary Approach ◽  
Smell Test ◽  
Significant Difference ◽  
Before And After

Olfactory dysfunction is a frequent non-motor symptom of Parkinson’s disease (PD) that involves deficits in odour detection, discrimination, and identification. Hyposmia may be related to neuronal degeneration with deposition of alpha-synuclein in primary olfactory areas as a very early component of the pathology of PD. Olfactory dysfunction also known as Gandhajnana or Gandhanaasha in Ayurveda is a result of improper functioning of different Vatasdue to either degeneration of Dhathus (Tissues) or obstruction in the normal movement of Vata. We analysed the smell test results within the population of Parkinsons patients admitted in Department of Neurology and Complementary medicine in Evangelical Hospital Hattingen from 2012 till 2017. Patients received the prescribed Allopathy and Ayurveda treatment for their ailments along with Ayurveda diet, Ayurveda massage and purification therapies. The primary and the only outcome measure was to assess the results of smelling sensation of the Parkinson’s patients already conducted by a Smell test with Sniffing Sticks supplied by Burghart Messtechnik. A paired t-test was conducted to compare scores obtained in smell test before and after treatment in each group separately. There was a significant difference in the scores of smell test in two groups. Results suggest that patients, treated first with Vasthi and then Ksheerabala oil Nasya showed significant improvement in the scores of smell test (t=-2.509, p= 0.017). The results of patients, treated with only Vasthi also showed significant improvement in the scores of smell test (t=-2.007, p= 0.053).

Identification of Frequent Differentially Methylated Region in Sporadic Bladder Cancers

2014 ◽  
Vol 94 (4) ◽  
pp. 479-484 ◽  
Author(s):  
Ryo Hasegawa ◽  
Kyoko Fujiwara ◽  
Daisuke Obinata ◽  
Hiroyuki Kawashima ◽  
Yui Shinojima ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bladder Cancer ◽  
Genomic Dna ◽  
Differentially Methylated Region ◽  
Low Grade ◽  
Aberrant Methylation ◽  
High Grade ◽  
Cpg Sites ◽  
Intron 1 ◽  
Exon 1

Introduction: Aberrant methylation levels in the cytosine-phosphate-guanine island (CpGi) region from exon 1 to intron 1 of the zygote arrest 1 (ZAR1) gene have been reported in several types of human cancers, including melanoma, brain tumor, and hepatocellular carcinoma. In the present study, methylation levels at the CpGi of ZAR1 exon 1/intron 1 in bladder cancer specimens were analyzed using mass spectrometry. Materials and Methods: Genomic DNA was extracted from 20 sporadic bladder cancers, and the methylation levels at ZAR1 CpGi were quantitatively examined by the MassARRAY EpiTYPER method. Result: The methylation levels at specific CpG sites of the ZAR1 CpGi were significantly lower in high-grade bladder cancers than in low-grade tumors. Conclusions: The results of the present study indicated a decreased methylation level at CpG sites of ZAR1 exon 1/intron 1. CpGi could serve as a biomarker for invasive bladder cancer.

scholarly journals A gene-to-gene interaction between aromatase and estrogen receptors influences bone mineral density

2006 ◽  
Vol 155 (1) ◽  
pp. 53-59 ◽  
Author(s):  
José A Riancho ◽  
María T Zarrabeitia ◽  
Carmen Valero ◽  
Carolina Sañudo ◽  
Verónica Mijares ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Estrogen Receptors ◽  
Postmenopausal Women ◽  
Bone Mineral ◽  
Promoter Region ◽  
Gene Interaction ◽  
Strong Linkage Disequilibrium ◽  
Mineral Density ◽  
Allelic Variants ◽  
Intron 1

Objective: The aromatization of androgenic precursors is the main source of estrogens in postmenopausal women. We tested the hypothesis that allelic variants of the genes coding for aromatase and estrogen receptors (ER) could interact to determine the estrogenic signals on the bone tissue and, consequently, bone mineral density (BMD). Design: Cross-sectional study including 331 postmenopausal women. Methods: BMD was measured by dual energy x-ray absorptiometry. A CG polymorphism of the aromatase gene as well as three polymorphisms of ERα (a TA repeat in the promoter region, a C T single nucleotide polymorphism (SNP) in intron 1 and an AG SNP in exon 8) and a CA repeat polymorphism of ERβ were studied. Results: Age, body weight and the aromatase genotype were associated with BMD. Allelic variants of ERβ and the exon 8 of ERα did not show a significant association with BMD. The polymorphisms located on the promoter and intron 1 of ERα interacted strongly with aromatase. Thus, in women TT homozygous for the ERα gene, there was a marked influence of aromatase genotypes on BMD: spine BMD was 0.724±0.027 g/cm2 in women with CC aromatase alleles and 0.926±0.032 g/cm2 in those with GG alleles (P<0.001). Hip BMD in women with CC and GG aromatase genotypes was 0.722±0.020 and 0.842±0.026 g/cm2 respectively (P=0.002). On the contrary, there were no aromatase-related differences in BMD in women with CT/CC alleles of ERα. Similarly, aromatase-related differences in BMD were found in women with short alleles at the promoter region of ERα, but not in those with long alleles. Both ERα polymorphisms were in strong linkage disequilibrium (P<0.001). Conclusion: These results suggest that the interaction between polymorphisms of genes involved in estrogen synthesis and estrogen signaling exerts an important influence on BMD in postmenopausal women, thus helping to explain, in part, its heritable component. Nevertheless, further studies are warranted to confirm this gene-to-gene interaction in other populations.

scholarly journals A single nucleotide polymorphism in the 3′UTR of the SNCA gene encoding alpha-synuclein is a new potential susceptibility locus for Parkinson disease

2009 ◽  
Vol 461 (2) ◽  
pp. 196-201 ◽  
Author(s):  
Sotiria Sotiriou ◽  
Gretchen Gibney ◽  
Andreas D. Baxevanis ◽  
Robert L. Nussbaum
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Parkinson Disease ◽  
Alpha Synuclein ◽  
Susceptibility Locus ◽  
Nucleotide Polymorphism ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Snca Gene
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