RESUMO
In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.
Assuntos
Família , Mutação/genética , Transtornos Parkinsonianos/genética , Adulto , Sequência de Aminoácidos , Sequência de Bases , Éxons/genética , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Monoéster Fosfórico Hidrolases/genética , Proteínas Quinases/genética , Ubiquitina-Proteína Ligases/genética , Adulto JovemRESUMO
Neurological disorders include a wide variety of mostly multifactorial diseases related to the development, survival, and function of the neuron cells. Single-nucleotide polymorphisms (SNPs) have been extensively studied in neurological disorders, and in a number of instances have been reproducibly linked to disease as risk factors. The RIT2 gene has been recently shown to be associated with a number of neurological disorders, such as Parkinson's disease (PD) and autism. In the study reported here, we investigated the association of the rs12456492 and rs16976358 SNPs of the RIT2 gene with PD, essential tremor (ET), autism, schizophrenia (SCZ), and bipolar disorder (BPD; total of 2290 patients), and 1000 controls, by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant association was observed between rs12456492 and two disorders, PD and ET, whereas rs16976358 was found to be associated with autism, SCZ, and BPD. Our findings are indicative of differential association between the RIT2 SNPs and different neurological disorders.
Assuntos
Predisposição Genética para Doença , Proteínas Monoméricas de Ligação ao GTP/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Povo Asiático/genética , Transtorno Autístico/genética , Transtorno Bipolar/genética , Tremor Essencial/genética , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/genética , Reação em Cadeia da Polimerase/métodos , Fatores de RiscoRESUMO
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Prevalence of PD increases steadily with age. A recent meta-analysis of genome-wide association studies has identified six new loci to be linked with PD. Here we investigated the association of four of these new loci, SIPA1L2, MIR4697, GCH1 and VPS13C with PD in an Iranian population. Through a case-control study a total of 1800 subjects comprising 600 PD patients and 1200 unrelated healthy controls were recruited. Rs10797576, rs329648, rs11158026 and rs2414739 related to SIPA1L2, MIR4697, GCH1 and VPS13C loci respectively, were genotyped in all subjects. The difference of genotype and allele frequencies between case and control groups were investigated using chi-square test and logistic regression models with R software. Genotype and allele frequencies were significantly different in PD patients and control group for rs329648, rs11158026 and rs2414739 (p-value=0.018, 0.025, and 0.009 respectively for allele frequency differences). There was no difference in genotype nor allele frequencies between the two groups for rs10797576. We replicated the association of three new loci which are proposed for PD. More studies in other populations and also functional analysis are required to clear the role of these variants in PD.
Assuntos
GTP Cicloidrolase/genética , Proteínas Ativadoras de GTPase/genética , Predisposição Genética para Doença/genética , MicroRNAs/genética , Proteínas Nucleares/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-IdadeRESUMO
Breast cancer (BC) is the most common cancer and the second cause of mortality in women all around the world. It is caused by several factors including genetic determinants, so that both genetic susceptibility factors and environmental factors are involved in the etiology. Significance of genes functioning in steroid hormone synthesis and metabolism are well established in breast cancer susceptibility. In this study, 134 women with BC and 135 normal controls were analyzed for their genotypes for the polymorphisms, rs743572, rs10046 and rs4646903, resided in CYP17, CYP19 and CYP1A1 genes, respectively. Significant differences in distributions of allele and genotype frequencies were found for the rs10046 polymorphism in CYP19 (p-value=0.01, OR (CI 95%) =1.59 (1.1-2.3), p-value=0.04, OR (CI 95%) =1.7 (1.1-2.5) respectively). For rs743,572 and rs 4646903 polymorphisms, no significant associations were observed. A significant association was observed between the rs10046 polymorphism of the CYP19gene and breast cancer in Iranian patients. Due to inconsistent previous results, more studies in different populations with larger sample sizes are indicated.
Assuntos
Aromatase/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Citocromo P-450 CYP1A1/genética , Polimorfismo de Nucleotídeo Único/genética , Esteroide 17-alfa-Hidroxilase/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , PrognósticoRESUMO
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. Both genetic and environmental factors are involved in the etiology of the disease. Many studies have revealed the susceptibility genes and variations for PD which need further confirmation. Here we evaluated the association of variations in SNCA, HUSEYO and CSMD1 genes with PD. A case-control study was conducted with 489 PD patients and 489 healthy controls. DNA was extracted from peripheral blood of all subjects and rs356220 and rs11931074 in SNCA, rs2338971 in HUSEYO and rs12681349 in CSMD1 were genotyped using PCR-RFLP method. The genotypes and allele frequencies were significantly different between case and control groups for rs356220, rs11931074 and rs2338971 but not for rs12681349. We provided further evidence that rs356220 is associated with increased risk of PD supporting previous studies in Caucasian-based and Japanese populations. The association of rs11931074 with decreased risk of PD was also significant. This study revealed the first evidence of the association of rs2338971 with increased risk of PD in the Iranian population. Nevertheless, these findings need further validation via more replication studies.
Assuntos
Heterogeneidade Genética , Predisposição Genética para Doença/genética , Proteínas de Membrana/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , alfa-Sinucleína/genética , Idoso , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Proteínas Supressoras de TumorRESUMO
A recent large-scale study have reported that rs1063843, a single nucleotide polymorphism located in the CAMKK2 gene is highly associated with schizophrenia in European and Han Chinese populations. Increasing evidences show that schizophrenia and bipolar disorder have some common genetic variance. Here, we evaluated the association of this variant with schizophrenia and bipolar disorder in Iranian population. Genomic DNA was extracted from peripheral blood of 500 schizophrenic patients, 500 bipolar patients and 500 normal controls and all were genotyped for the rs1063843 using a PCR-RFLP method. The allele frequency of rs1063843 was significantly different in both schizophrenia and bipolar patients comparing to control group. For the first time, we showed that rs1063843 is highly associated with bipolar disorder, although more replication studies are needed to confirm our findings. Our results also support the findings of previous studies suggesting a significant association between rs1063843 and schizophrenia.
Assuntos
Transtorno Bipolar/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Predisposição Genética para Doença/genética , Adulto , Povo Asiático/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genéticaRESUMO
DNA variations in the fibroblast growth factor 20 gene have been reported to be associated with Parkinson's disease (PD). The rs12720208, a functional SNP located in the 3'UTR region of the gene, was reported as a risk factor for PD. A number of studies, which tried to replicate the result in different populations, failed to detect any associations. In this study, we genotyped rs2720208 SNP in 520 PD patients and 520 healthy controls both from Iran. Significant differences were found in allele and genotype frequencies between patients and controls (p<0.0001 for both). Our results suggest that the rs12720208 polymorphism may be a risk factor for PD in Iranian population.
