Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Porto Alegre, 91501-970, Brazil.
Centros de Pesquisa Clínica e Experimental, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-903, Brazil.
Cerebellum. 2024 Dec;23(6):2217-2225. doi: 10.1007/s12311-024-01717-7. Epub 2024 Jul 6.
The age at onset (AO) of Machado-Joseph disease (SCA3/MJD), a disorder due to an expanded CAG repeat (CAGexp) in ATXN3, is quite variable and the role of environmental factors is still unknown. Caffeine was associated with protective effects against other neurodegenerative diseases, and against SCA3/MJD in transgenic mouse models. We aimed to evaluate whether caffeine consumption and its interaction with variants of caffeine signaling/metabolization genes impact the AO of this disease.
a questionnaire on caffeine consumption was applied to adult patients and unrelated controls living in Rio Grande do Sul, Brazil. AO and CAGexp were previously determined. SNPs rs5751876 (ADORA2A), rs2298383 (ADORA2A), rs762551 (CYP1A2) and rs478597 (NOS1) were genotyped. AO of subgroups were compared, adjusting the CAGexp to 75 repeats (p < 0.05).
171/179 cases and 98/100 controls consumed caffeine. Cases with high and low caffeine consumption (more or less than 314.5 mg of caffeine/day) had mean (SD) AO of 35.05 (11.44) and 35.43 (10.08) years (p = 0.40). The mean (SD) AO of the subgroups produced by the presence or absence of caffeine-enhancing alleles in ADORA2A (T allele at rs5751876 and rs2298383), CYP1A2 (C allele) and NOS1 (C allele) were all similar (p between 0.069 and 0.516).
Caffeine consumption was not related to changes in the AO of SCA3/MJD, either alone or in interaction with protective genotypes at ADORA2A, CYP1A2 and NOS1.
亨廷顿舞蹈病（SCA3/MJD）的发病年龄（AO）差异较大，其病因是 ATXN3 中 CAG 重复扩增（CAGexp）。环境因素的作用尚不清楚。咖啡因与其他神经退行性疾病以及转基因小鼠模型中的 SCA3/MJD 具有保护作用。我们旨在评估咖啡因的摄入及其与咖啡因信号转导/代谢基因变体的相互作用是否会影响该疾病的 AO。
我们向居住在巴西南里奥格兰德州的成年患者和无血缘关系的对照者发放了一份关于咖啡因摄入的问卷。先前已确定 AO 和 CAGexp。对 rs5751876（ADORA2A）、rs2298383（ADORA2A）、rs762551（CYP1A2）和 rs478597（NOS1）的 SNP 进行了基因分型。对亚组的 AO 进行了比较，并将 CAGexp 调整至 75 个重复（p<0.05）。
171/179 例病例和 98/100 例对照者摄入了咖啡因。高咖啡因摄入（每天多于 314.5mg 咖啡因）和低咖啡因摄入（每天少于 314.5mg 咖啡因）的病例的平均（标准差）AO 分别为 35.05（11.44）和 35.43（10.08）年（p=0.40）。ADORA2A（rs5751876 和 rs2298383 的 T 等位基因）、CYP1A2（C 等位基因）和 NOS1（C 等位基因）中咖啡因增强等位基因的存在或缺失所产生的亚组的平均（标准差）AO 均相似（p 在 0.069 到 0.516 之间）。
咖啡因的摄入与 SCA3/MJD 的 AO 变化无关，无论是单独摄入还是与 ADORA2A、CYP1A2 和 NOS1 的保护基因型相互作用。
