RESUMO
BACKGROUND: Subcortical vascular dementia (SVaD) is a common form of dementia, attributed to ischemic small-vessel disease. Blood viscosity (BV) may contribute to the pathophysiology of SVaD. However, SVaD patients with coexisting amyloid deposition may not show differences in BV because their small-vessel disease may result from amyloid angiopathy independently of BV. We, therefore, hypothesized that BV might show different changes compared with control subjects in subcortical vascular mild cognitive impairment (svMCI) that refers to the prodromal stage of SVaD according to cerebral amyloid burden detected by the [(11)C] Pittsburgh compound B (PiB) PET (positron emission tomography), and apolipoprotein 4 (ApoE4) genotype (a known risk factor for vascular and parenchymal amyloid). METHODS: Our subjects consisted of 33 healthy normal controls (NC), 28 patients with PiB(-) svMCI, and 12 with PiB(+) svMCI. They underwent scanning capillary tube viscometer measuring BV during systolic and diastolic phases. RESULTS: Compared with the NC group, the PiB(-) svMCI group showed increased diastolic blood viscosity (DBV) but no difference in systolic blood viscosity (SBV). By contrast, there was no significant difference in SBV and DBV between the NC and PiB(+) svMCI groups. Within the PiB(+) svMCI group, ApoE4(-) subgroup showed increased DBV compared with the ApoE4(+) subgroup. CONCLUSIONS: Increased DBV is an important contributor to the development of "pure" svMCI (ie, without cerebral amyloid deposition). The relationship between BV and PiB(+) svMCI differed according to ApoE genotype, suggesting that the pathogenesis of PiB(+) svMCI might also be heterogeneous.
Assuntos
Viscosidade Sanguínea , Angiopatia Amiloide Cerebral/sangue , Disfunção Cognitiva/sangue , Demência Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Apolipoproteína E4/genética , Estudos de Casos e Controles , Angiopatia Amiloide Cerebral/diagnóstico , Angiopatia Amiloide Cerebral/genética , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/genética , Demência Vascular/diagnóstico , Demência Vascular/genética , Feminino , Predisposição Genética para Doença , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fenótipo , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Estudos Prospectivos , Compostos Radiofarmacêuticos , Fatores de Risco , TiazóisRESUMO
BACKGROUND: Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention. METHODS AND RESULTS: We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (ALMS1) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI. CONCLUSIONS: The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI.