RESUMO
Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform. The genotypic and allelic distributions of MEF2D rs2274316 and ASTN2 rs6478241 were significantly different between migraine patients and controls. Univariate and multivariate analysis revealed significant associations of polymorphisms in the MEF2D and ASTN2 genes with migraine susceptibility. MEF2D, PRDM16 and ASTN2 were also found to be associated with migraine without aura (MO) and migraine with family history. And, MEF2D and ASTN2 also served as genetic risk factors for the migraine without family history. The generalized multifactor dimensionality reduction analysis identified that MEF2D and HTR2E constituted the two-factor interaction model. Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially MO, among Chinese patients. It appears that there is no association with serotonin receptor related genes.
Assuntos
Proteínas de Ligação a DNA/genética , Glicoproteínas/genética , Transtornos de Enxaqueca/genética , Proteínas do Tecido Nervoso/genética , Fatores de Transcrição/genética , Adulto , Alelos , China , Proteínas de Ligação a DNA/efeitos dos fármacos , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fatores de Transcrição MEF2/genética , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/patologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fatores de Transcrição/efeitos dos fármacosRESUMO
The inverse association of the functional ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y variant with Parkinson's disease (PD) among Caucasian populations has been debated. We conducted a large-scale analysis to investigate the age-of-onset effect of the UCHL1 variant in PD among ethnic Chinese. Individual data sets from 5 centers comprising a total of 4088 study subjects were analyzed. In the univariate analysis, only data from 1 center showed a trend towards a protective effect among young subjects. However, in the combined analysis, no significant association between the UCHL1 variant and PD was detected (A allele frequency 0.531 vs. 0.528, p=0.87, OR 1.01, 95% CI 0.92-1.1). Among subjects less than 60 years old, the OR is 0.99 (95% CI 0.84-1.16, p=0.88). A multivariate logistic regression analysis showed that family history, UCHL1 variant and the interaction of UCHL1 variant and age at onset (p=0.816) were not significantly associated with PD.
Assuntos
Variação Genética/genética , Doença de Parkinson/enzimologia , Doença de Parkinson/genética , Ubiquitina Tiolesterase/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , Povo Asiático/genética , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Singapura/epidemiologia , Singapura/etnologia , Taiwan/epidemiologia , Taiwan/etnologia , Ubiquitinação/genética , Adulto JovemRESUMO
Mutations in GBA gene have been reported to be in patients with Parkinson's disease (PD) from different ethnic populations, including Taiwanese Chinese. To explore whether mutation in GBA is also associated with PD in Mainland China, we have now a case control study. The occurrence of the GBA L444P mutation was analyzed in an independent cohort of PD patients and controls from Mainland China. This mutation was present in 20/616 (3.2%) of PD compared with 1/411 (0.2%) of controls (odds ratio, OR=13.76, 95% Confidence interval, CI: 1.84-102.92, p=0.001). All carriers harbored the heterozygous genotype. In a subset analysis, the frequency of this mutation was higher both in early onset (EOPD) and late onset PD (LOPD) than in controls. However, no difference in clinical characteristics, such as gender, age at onset, onset symptoms, Hoehn-Yahr stage and UPDRS, was found between L444P carriers and non-carriers. In addition, we also explored the potential relationship between GBA L444P mutation and LRRK2 G2385R and R1628P variants in patients with PD. But no association was found, either. In conclusion, our data suggest that the GBA L444P mutation plays an important role in the development of PD also in Han-Chinese patients from Mainland China.
Assuntos
Glucosilceramidase/genética , Mutação de Sentido Incorreto , Doença de Parkinson/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Estudos de Casos e Controles , China , Estudos de Coortes , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/genética , Adulto JovemAssuntos
Substituição de Aminoácidos/genética , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologiaRESUMO
Mutation in UCH-L1 has been reported as a rare cause of autosomal dominant Parkinson's disease (PD). A S18Y polymorphism in the same gene has been associated with sporadic PD. We investigated the frequency of this polymorphism among the Han-Chinese ethnic population in a case-control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. We did not observe any difference in allele or genotype frequencies between the cases and the controls (P>0.05). Our results do not support a role for this variant in sporadic PD.
Assuntos
Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Ubiquitina Tiolesterase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been recently linked with autosomal-dominant parkinsonism, and polymorphisms have been commonly associated with sporadic Parkinson's disease (PD). A p.2385G>R variant has been reported as a risk factor for PD in Taiwan, Singapore and Japan. Herein, we have assessed the frequency of this polymorphism among the ethnic Han-Chinese population in a case-control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. Hardy-Weinberg equilibrium of each group was calculated, and differences in genotype frequencies between groups were assessed by the Chi-square test. In the PD cohort, 70 patients (11.7%) were heterozygous and 1 (0.2%) was homozygous for the p.2385G>R variant. This was significantly more frequent than in the controls [3.3%, Odds ratio = 3.9, 95% confidence interval (CI) = 2.1-7.5, P < 0.01]. Clinically, the age of PD onset of the p.2385G>R carriers was lower than the non-carriers (P = 0.01). Our study indicates that this LRRK2 p.2385G>R substitution contributes to the development of PD in ethnic Han-Chinese population, which may play important implications for future study on molecular genetics and pathogenesis of PD.
