RESUMO
It has been reported that some single-nucleotide polymorphisms (SNPs) are associated with the risk of Parkinson's disease (PD), but whether a combination of these SNPs would have a stronger association with PD than any individual SNP is unknown. Sixteen SNPs located in the 8 genes and/or loci (SNCA, LRRK2, MAPT, GBA, HLA-DR, BST1, PARK16, and PARK17) were analyzed in a Chinese cohort consisting of 1061 well-characterized PD patients and 1066 control subjects from Central South of Mainland China. We found that Rep1, rs356165, and rs11931074 in SNCA gene; G2385R in LRRK2 gene; rs4698412 in BST1 gene; rs1564282 in PARK17; and L444P in GBA gene were associated with PD with adjustment of sex and age (p < 0.05) in the analysis of 16 variants. PD risk increased when Rep1 and rs11931074, G2385R, rs1564282, rs4698412; rs11931074 and G2385R, rs1564282, rs4698412; G2385R and rs1564282, rs4698412; and rs1564282 and rs4698412 were combined for the association analysis. In addition, PD risk increased cumulatively with the increasing number of variants (odds ratio for carrying 3 variants, 3.494). In summary, we confirmed that Rep1, rs356165, and rs11931074 in SNCA gene, G2385R in LRRK2 gene, rs4698412 in BST1 gene, rs1564282 in PARK17, and L444P in GBA gene have an independent and combined significant association with PD. SNPs in these 4 genes have a cumulative effect with PD.
Assuntos
Povo Asiático/genética , Estudos de Associação Genética , Herança Multifatorial/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , ADP-Ribosil Ciclase/genética , Adolescente , Adulto , Idoso , Antígenos CD/genética , Estudos de Coortes , Feminino , Proteínas Ligadas por GPI/genética , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/genética , Adulto Jovem , alfa-Sinucleína/genéticaRESUMO
Autosomal dorminant Parkinson's disease (ADPD) has been associated with mutations in the SCNA, LRRK2, UCHL1, HtrA2 and GIGYF2 genes. We studied the prevalence of variants in all five genes in 12 Chinese unrelated families with ADPD and 4 families with both essential tremor (ET) and Parkinson's disease (PD) phenotypes using direct sequencing analysis. We found 27 variants in the LRRK2 gene, eight in GIGYF2 gene, three in the SCNA and UCHL1 gene respectively, in which five variants were novel. However, no pathogenic mutations in the five genes were found in these families. Our result indicated that SCNA, LRRK2, UCHL1, HtrA2 and GIGYF2 genes' mutations might not be a main reason for Chinese ADPD.
Assuntos
Povo Asiático/genética , Proteínas de Transporte/genética , Proteínas Mitocondriais/genética , Transtornos Parkinsonianos/genética , Proteínas Serina-Treonina Quinases/genética , Serina Endopeptidases/genética , Canais de Sódio/genética , Ubiquitina Tiolesterase/genética , Sequência de Bases , Análise Mutacional de DNA , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The Grb10-interacting GYF protein-2 gene (GIGYF2) is a PARK11 gene that reportedly has a causal role in familial Parkinson's disease (PD) among populations from Italy and France. However, no comprehensive study of the GIGYF2 gene has been conducted among PD patients from mainland China. In our previous study, the GIGYF2 gene was directly sequenced, and nine missense variants and 14 polymorphisms were identified. For these 14 polymorphisms, in the present study we performed a casecontrol analysis for 300 PD patients and 200 healthy controls from mainland China. The c.297T>C p.Ala99Ala polymorphism was associated with increased risk with respect to the pathogenesis of sporadic PD. In conclusion, within the Chinese population, the c.297T>C p.Ala99Ala polymorphism of the GIGYF2 gene may be associated with an increased risk of developing PD.
Assuntos
Proteínas de Transporte/genética , Predisposição Genética para Doença , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Seguimentos , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A recent study has shown that FBXO7 is a causative gene for PARK15-linked autosomal recessive early-onset Parkinsonism which was described by Davison for the first time in 1954 and known as Pallido-Pyramidal Disease or Parkinsonia-Pyramidal Syndrome in the past. In order to investigate the characteristics of FBXO7 gene mutations in Chinese early-onset Parkinsonism patients, we performed polymerase chain reaction and DNA direct sequencing on 135 patients and 200 controls. In this study, we found 10 polymorphisms including two novel polymorphisms (-274G-->C, c.A155G), but no pathogenetic mutations in the FBXO7 gene were detected. This suggests that FBXO7 mutations may be rare in Chinese early-onset Parkinsonism patients.
Assuntos
Proteínas F-Box/genética , Transtornos Parkinsonianos/genética , Adulto , Idade de Início , Povo Asiático , China , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Mutação , Polimorfismo GenéticoRESUMO
The Grb10-Interacting GYF Protein-2 gene (GIGYF2), located in the chromosomal region 2q36-q37, has been reported as a PARK11 gene with a causal role in familial Parkinson's disease (PD) in Italian and French populations. However, there is no comprehensive study of GIGYF2 gene conducted in Chinese patients with PD from mainland China. The 27 coding exons and intron/exon boundaries of the GIGYF2 gene were sequenced in 300 sporadic patients with Parkinson's disease. Eight heterozygous and one homozygous novel missense variants were identified in nine patients with PD, and not in 300 controls. p.Leu580Phe locates in the GYF domain and might interrupt the potentially function of GIGYF2 protein. Another variant Gln979stop encodes a truncated protein. In conclusion, we identified nine novel variants in GIGYF2 gene, which might be associated with PD in the Chinese population.
