Martins Ana Carolina, Furtado Gabriel Vasata, Pinheiro Jordânia Dos Santos, Saraiva-Pereira Maria Luiza, Jardim Laura Bannach
Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Centros de Pesquisa Clínica e Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Mov Disord Clin Pract. 2025 Apr;12(4):520-526. doi: 10.1002/mdc3.14338. Epub 2025 Jan 20.
Machado-Joseph disease (SCA3/MJD) is a neurodegenerative condition caused by a dominant expansion of a CAG repeat (CAGexp). Most of the variability in the age at onset of symptoms (AO) remains unexplained, and environmental influences were scarcely studied.
The objective was to test if AO of SCA3/MJD carriers can be associated with markers of the rural environment, such as demographic density (DeD), proportion of rural population (PRP), and the consumption of untreated well water (CWW).
Symptomatic subjects from Rio Grande do Sul, Brazil, diagnosed between 1999 and 2017, and living in the same municipalities where they were born, were included, provided their CAGexp and AO were available, and the residual AO (RAO) could be estimated. DeD, PRP, and CWW were obtained from the Brazilian Census of 2010. Participants were stratified in high versus low DeD, PRP, and CWW groups, and their RAOs were compared for a P < 0.05.
A total of 188 subjects were studied. The mean (SD) RAOs of subjects from low and high DeD groups were -1.90 (6.98) and -0.11 (6.20) (P = 0.046); from low and high PRP groups were -0.12 (6.20) and -1.90 (6.99) (P = 0.046); and from low and high CWW groups were -0.11 (6.04) and -1.89 (7.11) (P = 0.034).
AO of SCA3/MJD carriers was earlier in groups related to rural life. Our evidence suggests the presence of a risk factor in the rural environment, for earlier onset of symptoms in SCA3/MJD.
马查多-约瑟夫病(SCA3/MJD)是一种由CAG重复序列(CAGexp)显性扩增引起的神经退行性疾病。症状发作年龄(AO)的大部分变异性仍无法解释,且对环境影响的研究很少。
目的是检验SCA3/MJD携带者的AO是否与农村环境指标相关,如人口密度(DeD)、农村人口比例(PRP)和未处理井水的消费量(CWW)。
纳入1999年至2017年间在巴西南里奥格兰德州被诊断出患有该病、居住在其出生的同一城市、且可获得其CAGexp和AO数据,并能估算出残余AO(RAO)的有症状受试者。DeD、PRP和CWW数据来自2010年巴西人口普查。参与者被分为DeD、PRP和CWW的高值组和低值组,并比较他们的RAO,P < 0.05具有统计学意义。
共研究了188名受试者。DeD低值组和高值组受试者的平均(SD)RAO分别为-1.90(6.98)和-0.11(6.20)(P = 0.046);PRP低值组和高值组分别为-0.12(6.20)和-1.90(6.99)(P = 0.046);CWW低值组和高值组分别为-0.11(6.04)和-1.89(7.11)(P = 0.034)。
SCA3/MJD携带者的AO在与农村生活相关的组中出现得更早。我们的证据表明农村环境中存在一个危险因素,可导致SCA3/MJD症状更早出现。