RESUMO
BACKGROUND: Recently, rs2421947 in DNM3 (dynamin 3) was reported as a genetic modifier of age at onset (AAO) of LRRK2 G2019S-related Parkinson's disease (PD) in a genome-wide association study in Arab-Berber population. Rs356219 in SNCA (α-synuclein) was also reported to regulate the AAO of LRRK2-related PD in European populations, and GAK (Cyclin G-associated kinase) rs1524282 was reported to be associated with an increased PD risk with an interaction with SNCA rs356219. G2019S variant is rare in Asian populations, whereas two other Asian-specific LRRK2 variants, G2385R and R1628P, are more frequent with a twofold increased risk of PD. METHODS: In this study, we investigated whether rs2421947, rs356219 and rs1524282 modified AAO in LRRK2-related PD patients in Han Chinese population. We screened LRRK2 G2385R and R1628P variants in 732 PD patients and 1992 healthy controls, and genotyped DNM3 rs2421947, SNCA rs356219 and GAK rs1524282 among the LRRK2 carriers. RESULTS: The SNCA rs356219-G allele was found to increase the risk of PD in LRRK2 carriers (OR 1.50, 95%CI 1.08-2.01, P = 0.016), and the AAO of AG + GG genotypes was 4 years earlier than AA genotype (P = 0.006). Nonetheless, no similar association was found in DNM3 rs2421947 and GAK rs1524282. CONCLUSIONS: Our results show that SNCA but not DNM3 or GAK is associated with AAO of LRRK2-PD patients in Chinese population.
Assuntos
Dinamina III/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , alfa-Sinucleína/genética , Idade de Início , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Vigilância da PopulaçãoRESUMO
Recently, mutations of DNAJC12 gene were reported to be associated with early-onset parkinsonism, progressive neurodevelopmental delay, and dystonia in several unrelated pedigrees. This study aimed to evaluate DNAJC12 coding mutations in sporadic Chinese Han patients with Parkinson's disease (PD) and test whether an age-of-onset effect exists. Seven hundred two Chinese Han sporadic PD patients, including 181 early-onset PD and 521 late-onset PD, and 728 healthy controls were recruited. No documented disease-causing mutation of DNAJC12 was identified, but we found 7 single-nucleotide polymorphisms. Allele frequencies did not differ between all the PD patients and controls or between any 2 subgroups for all these single-nucleotide polymorphisms. Our study suggests that DNAJC12 mutation is not a risk factor of PD in Chinese Han population, and no age-of-onset effect was verified.
