RESUMO
Familial idiopathic basal ganglia calcification (FIBGC) is an inherited neurodegenerative disorder characterized by the accumulation of calcium deposits in different brain regions, particularly in the basal ganglia. FIBGC usually follows an autosomal dominant pattern of inheritance. Despite the mapping to chromosome 14q of a susceptibility locus for IBGC (IBCG1) in one family, this locus has been excluded in several others, demonstrating genetic heterogeneity in this disorder. The etiology of this disorder thus remains largely unknown. Using a large extended multigenerational Italian family from South Tyrol with 17 affected in a total of 56 members, we performed a genome-wide linkage analysis in which we were able to exclude linkage to the IBCG1 locus on chromosome 14q and obtain evidence of a novel locus on chromosome 2q37. Electronic supplementary material. The online version of this article (doi:10.1007/s12031-009-9287-3) contains supplementary material, which is available to authorized users.
Assuntos
Doenças dos Gânglios da Base/genética , Calcinose/genética , Cromossomos Humanos Par 2/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Doenças dos Gânglios da Base/metabolismo , Doenças dos Gânglios da Base/fisiopatologia , Calcinose/metabolismo , Calcinose/fisiopatologia , Transtornos Cromossômicos/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 14/genética , Análise Mutacional de DNA , Feminino , Genes Dominantes/genética , Ligação Genética/genética , Marcadores Genéticos/genética , Testes Genéticos , Variação Genética/genética , Humanos , Padrões de Herança/genética , Itália , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
An inverse association between coffee and Parkinson's disease (PD) has been reported. However, it remains uncertain why some but not all coffee drinkers are less susceptible to PD. We considered the possibility of a pharmacogenetic effect. In our study, we included 1,208 subjects (446 case-unaffected sibling pairs and 158 case-unrelated control pairs) recruited from an ongoing study of the molecular epidemiology of PD in the Upper Midwest (USA). We collected information on lifetime coffee drinking and we studied two genes: ADORA2A, which encodes the major receptor activity of caffeine in the brain (variants rs5751876 and rs3032740), and CYP1A2, which encodes the major rate-limiting step of caffeine metabolism (variants rs35694136 and rs762551). We did not observe significant associations of coffee drinking or of the genetic variants with PD susceptibility, either independently or jointly, in the sample overall and in most strata. Our study neither supports the hypothesis that coffee protects against PD nor provides evidence for a pharmacogenetic effect.