ABSTRACT
Late-onset Alzheimer's disease (LOAD) is a multifactorial neurodegenerative disorder that corresponds to most Alzheimer's disease (AD) cases. Inflammation is frequently related to AD, whereas microglial cells are the major phagocytes in the brain and mediate the removal of Aß peptides. Microglial cell dsyregulation might contribute to the formation of amyloid plaques, a hallmark of AD. Genome-wide association studies have reported genetic loci associated with the inflammatory pathway involved in AD. Among them, rs3865444 CD33, rs3764650 ABCA7, rs6656401 CR1, and rs610932 MS4A6A variants in microglial genes are associated with LOAD. These variants are proposed to participate in the clearance of Aß peptides. However, their association with LOAD was not validated in all case-control studies. Thus, the present work aimed to assess the involvement of CD33 (rs3865444), ABCA7 (rs3764650), CR1 (rs6656401), and MS4A6A (rs610932) with LOAD in a sample from southeastern Brazil. The genotype frequencies were assessed in 79 AD patients and 145 healthy elders matched for sex and age. We found that rs3865444 CD33 acts as a protective factor against LOAD. These results support a role for the inflammatory pathway in LOAD.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Alzheimer Disease/genetics , Membrane Proteins/genetics , Polymorphism, Single Nucleotide , Receptors, Complement 3b/genetics , Sialic Acid Binding Ig-like Lectin 3/genetics , Aged , Aged, 80 and over , Brazil , Case-Control Studies , Female , Gene Frequency , Humans , Male , Microglia/metabolismABSTRACT
Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings in Muenke syndrome. To better define the clinical features of this syndrome, we initiated a study of the natural history of Muenke syndrome. To date, we have conducted a standardized evaluation of nine patients with a confirmed Pro250Arg mutation in FGFR3. We reviewed audiograms from an additional 13 patients with Muenke syndrome. A majority of the patients (95%) demonstrated a mild-to-moderate, low frequency sensorineural hearing loss. This pattern of hearing loss was not previously recognized as characteristic of Muenke syndrome. We also report on feeding and swallowing difficulties in children with Muenke syndrome. Combining 312 reported cases of Muenke syndrome with data from the nine NIH patients, we found that females with the Pro250Arg mutation were significantly more likely to be reported with craniosynostosis than males (P < 0.01). Based on our findings, we propose that the clinical management should include audiometric and developmental assessment in addition to standard clinical care and appropriate genetic counseling.
Subject(s)
Craniosynostoses/diagnosis , Craniosynostoses/genetics , Hearing Loss, Sensorineural/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Adult , Aged , Audiometry/methods , Child, Preschool , Developmental Disabilities/diagnosis , Developmental Disabilities/genetics , Female , Hearing Loss, Sensorineural/diagnosis , Humans , Infant , Male , Mutation , Pedigree , Phenotype , Sex Factors , Speech Disorders/diagnosis , Speech Disorders/genetics , Syndrome , Tomography, X-Ray Computed/methodsSubject(s)
Humans , Male , Child, Preschool , Child , Adolescent , Adult , Muscular Dystrophies/genetics , Myotonic Dystrophy/genetics , Gene Deletion , MosaicismSubject(s)
Humans , Male , Female , Spinocerebellar Degenerations/genetics , Huntington Disease/geneticsABSTRACT
As atividades séricas das enzimas creatino-cinase (CK) e piruvato-cinase (PK) foram determinadas em 146 mulheres beterozigotas certas quanto ao gene da distrofia muscular de Duchenne (DMD) e 187 mäes de casos isolados, pertencentes a dois grupos raciais: caucasóide e negroide. A atividade da CK foi medida em 206 mulheres caucasoides e 127 mulheres negroides e a da PK em 148 caucasoides e 92 negroides. Os resultados desta pesquisa mostraram um aumento da média de atividade enzimática no grupo de mulheres heterozigotes e mäes de casos isolados negroides em comparaçäo ao grupo de mulheres caucasoides. Entretanto, as diferenças foram estatísticamente significantes apenas para a CK sérica. Sugere-se portanto, que os resultados da atividade sérica da CK de mulheres em risco de serem portadoras do gene da DMD sejam comparados com os de mulheres normais de mesmo grupo racial
Subject(s)
Humans , Female , Creatine Kinase/blood , Gene Frequency , Muscular Dystrophies/genetics , Pyruvate Kinase/blood , Black People , Carrier State , Cytogenetics , White People , Genetic Carrier Screening , Muscular Dystrophies/prevention & control , RiskABSTRACT
Os níveis da fosfatase alcalina placentária foram determinados em 433 amostras de plasma de parturientes, atendidas na Maternidade Tsylla Balbino em Salvador. Observou-se associaçäo significativa entre níveis baixos de atividade enzimática e menor peso do recém-nascido (F3.430 = p<0,05). A análise do efeito do hábito de fumar sobre os níveis da fosfatase alcalina placentária näo atingiu significância estatística quando mantido constante o peso do recém-nascido. Esse procedimento evita conclusöes espúrias relativas ao efeito do fumo sobre os níveis da enzima, uma vez que ambos estäo associados a baixo peso do recém-nascido. Todavia, considerando as alteraçöes estruturais que o fumo causa à placenta (22) näo será surpreendente que delas decorram diminuiçäo na produçäo e na liberaçäo da fosfatase alcalina placentária näo detectadas no presente trabalho. Os autores sugerem que a interaçäo entre hábito de fumar, níveis da fosfatase alcalina placentária no plasma materno e peso do recém-nascido necessita maiores investigaçöes
