Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-03-21T11:41:24Z No. of bitstreams: 1 ClarissaLoureiroCampeloBezerra_TESE.pdf: 6936560 bytes, checksum: 72a397096dabf519d649a5db63d55327 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-03-22T15:43:33Z (GMT) No. of bitstreams: 1 ClarissaLoureiroCampeloBezerra_TESE.pdf: 6936560 bytes, checksum: 72a397096dabf519d649a5db63d55327 (MD5) / Made available in DSpace on 2018-03-22T15:43:33Z (GMT). No. of bitstreams: 1 ClarissaLoureiroCampeloBezerra_TESE.pdf: 6936560 bytes, checksum: 72a397096dabf519d649a5db63d55327 (MD5) Previous issue date: 2017-03-14 / Crescentes evidencias indicam que a susceptibilidade gen?tica contribui para a etiologia da doen?a de Parkinson espor?dica (DP). Varia??es gen?ticas no gene SNCA, respons?vel pela codifica??o da alfa-sinucle?na, foram bem estabelecidas atrav?s de estudos de linkage e GWAS. Estudos em todo o mundo encontraram associa??o positiva com polimorfismos de nucleot?deo ?nico (SNPs) no gene SNCA e o aumento do risco para DP. Al?m disto, varia??es no SNCA podem influenciar caracter?sticas ou fen?tipos da DP espor?dica. Este estudo teve como objetivo investigar associa??es entre os SNPs no gene SNCA e a sintomatologia motora e n?o-motora da DP em uma popula??o brasileira. 206 sujeitos (grupo DP= 105 e grupo controle= 101) participaram do estudo. Os pacientes com DP foram recrutados no ambulat?rio de neurologia do Hospital Onofre Lopes, na cidade de Natal (RN). Foram utilizados question?rios e escalas para avaliar o hist?rico de sa?de, fatores ambientais, aspectos motores (Hoehn & Yarh e Unified Parkinson?s Disease Rating Scale), funcionais (Schwab & England), cognitivos (Bateria de Avalia??o Frontal e Mini-Exame do Estado Mental) e emocionais (Invent?rio de Depress?o de Beck e Inventario de Ansiedade de Beck) dos participantes. Tamb?m foi coletada uma amostra de sangue para a realiza??o da extra??o do DNA e posterior genotipagem dos SNPs rs11931074, rs356219, rs2583988, rs2736990. Quanto a avalia??o cl?nica, o grupo DP apresentou comprometimento motor de moderado a severo associado a uma moderada redu??o da capacidade funcional. Os d?ficits cognitivos foram mais presentes nos sujeitos com baixa escolariza??o. Os sintomas depressivos e ansiosos foram evidenciados com maior frequ?ncia e gravidade no grupo DP. Os dados da genotipagem mostraram todos os SNP mais frequentes no grupo DP, e a associa??o dos SNPs rs356219, rs2583988, rs2736990 aumentando o risco para DP foi confirmada. Tamb?m foi encontrada uma associa??o dos alelos de risco com a DP de in?cio precoce. T-rs2583988, G-rs356219 e C-2736990 foram significativamente mais frequentes nos pacientes com altera??es cognitivas quando comparados aos controles com a mesma condi??o. Al?m disto, a presen?a de altera??es cognitivas foi mostrou-se um fator preditivo para a DP em um modelo de regress?o log?stica. Este estudo ? o primeiro a demonstrar a associa??o de polimorfismos no gene SNCA em uma popula??o da Am?rica do Sul. / Increasing evidence indicate that genetic susceptibility contributes to the etiology of sporadic Parkinson?s Disease (PD). Genetic variations in SNCA gene, which encodes alpha-synuclein protein, are already well established in linkage and GWAS studies. Worldwide studies have find positive association of single nucleotide polymorphism (SNP) in SNCA and the increase risk for PD. In addition, variants in SNCA can influence individual traits or phenotypes of sporadic PD. The present study investigated associations between SNPs in SNCA gene and motor and non-motor symptoms of PD in a Brazilian population. 206 subjects (PD group= 105 and Control group = 101) participated in this study. The patients with PD were recruited from the neurology clinic of Onofre Lopes University Hospital, in Natal (RN, Brazil). We used questionnaires and scales to evaluate the healthy history, environmental factors, motor (Hoehn & Yarh e Unified Parkinson?s Disease Rating Scale), functional (Schwab & England), cognitive (Frontal Assessment Battery and Mini Mental State Examination) and emotional (Beck Depression Inventory and Beck Anxiety Inventory) aspects of the subjects. We also collected a blood sample to DNA extraction and genotyping of SNPs rs11931074, rs356219, rs2583988 and rs2736990. Regarding clinical assessment, the PD group presented motor impairment associated to a moderate decrease of functional capacity. The cognitive impairments were more evident in individuals with low education. Depressive and anxiety symptoms had a higher frequency and severity in PD group. All SNPs were more frequent in PD patients (p<0.05), and the associations of SNPs rs2583988, rs356219 and rs2736990 with increased PD risk were confirmed. The G-rs356219 and C-rs2736990 alleles had a significant higher frequency in patients with early onset PD. T-rs2583988, G-rs356219 and C-2736990 risk alleles were significantly more frequent in PD patients with cognitive impairments than controls in this condition. Furthermore, the presence of cognitive impairment was a predictor for PD in a logistic regression model. This study demonstrated for the first time an association of SNCA polymorphisms and PD in a South-American sample.