RESUMEN
TUSC3 interacts with the protein phosphatase 1 and magnesium ion transport system, which plays an important role in learning and memory. Abnormal conditions of learning and memory are common clinical characteristics of mental retardation (MR). However, the association of TUSC3 genetic polymorphisms with MR remains unknown. A total of 456 DNA samples including 174 nuclear families containing MR were collected in the Qinba mountain area of China. The genotypes of eight tag single nucleotide polymorphisms of TUSC3 were evaluated with traditional genetic methods. Family-based association tests, transmission disequilibrium tests (TDTs), and haplotype relative risk (HRR) analyses were performed to investigate the association between genetic variants of the TUSC3 gene and MR. The genetic polymorphisms rs10093881, rs6530893, and rs6994908 were associated with MR (all P values <0.05) based upon the results of single-site TDT and HRR analyses. The haplotype block consisting of rs6530893 and rs6994908, harboring the sixth exon of TUSC3, was also associated with MR (all P values <0.05). This study demonstrated an association between genetic polymorphisms of the TUSC3 gene and MR in the Qinba mountain area, the sixth exon of which might contribute to the risk of MR. However, further studies are needed on the causal mechanisms in this association.
Asunto(s)
Exones , Discapacidad Intelectual/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Proteínas Supresoras de Tumor/genética , Adolescente , Pueblo Asiatico , Niño , Preescolar , Femenino , Expresión Génica , Haplotipos , Humanos , Discapacidad Intelectual/etnología , Discapacidad Intelectual/fisiopatología , Pruebas de Inteligencia , Desequilibrio de Ligamiento , Masculino , Núcleo Familiar , RiesgoRESUMEN
FGD1 encoding a guanine nucleotide exchange factor, specifically activates Rho GTPase cell division cycle 42 (Cdc42). Dysfunction of FGD1 causes Aarskog-Scott syndrome (MIM #305400), an X-linked disorder that may affect bone and intellectual development. However, the relationship between FGD1 and intellectual developmental disorders (IDD) remains unclear. The purpose of this study was to investigate the genetic association between the FGD1 polymorphism and IDD. Working with families from the Qinba mountain area where the occurrence of IDD is higher than the average in China, we analyzed 456 samples from 130 nuclear families, effectively controlling for stratification and environmental factors. Five SNP loci (rs2230265, rs7881608, rs2239809, rs6614244, and rs2284710) were selected that were well distributed within the FGD1 gene. Genotyping was performed through single-strand conformation polymorphism and restriction fragment length polymorphism. The data were analyzed with transmission disequilibrium tests. In the Qinba mountain area, no significant association was observed between IDD and allele or genotype frequencies, or the haplotype of the 5 SNP loci of the FGD1 gene. The results indicate that FGD1 may not be a monogenetic X-linked factor in IDD. Further studies are required to investigate its role in intellectual development based on its specific interactions with Cdc42 or other partner proteins contributing to IDD.
Asunto(s)
Discapacidades del Desarrollo/genética , Factores de Intercambio de Guanina Nucleótido/genética , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , Niño , Preescolar , China , HumanosRESUMEN
Cauda equina syndrome (CES) is characterized by varying patterns of low back pain, sciatica, lower extremity sensorimotor loss, and bowel and bladder dysfunction. The prognosis for complete recovery of CES is dependent on not only the time before surgical intervention with decompression but also the severity of the nerve damage. Delayed or severe nerve compression impairs the capability of nerve regeneration. Transplantation of neural stem cells (NSCs) may facilitate axon regeneration and functional recovery in a spectrum of neurological disorders. Our study shows that the NSCs derived from early postnatal dorsal root ganglion (DRG) are able to proliferate to form neurospheres and differentiate into O4(+) oligodendrocytes but not glial fibrillary acidic protein (GFAP(+)) astrocytes or ßIII-tubulin(+) neurons in vitro. After intrathecal transplantation into the lumbar spinal canal stenosis animal model, most of the GFP-expressing NSCs were induced to differentiate into oligodendrocytes in vivo. Although the recovery of sensorimotor function was not significantly improved in rats with transplantation therapy, our results implied that subarachnoid microinjection of NSCs may promote axon regeneration of DRG neurons in the cauda equina model after nerve injury.
Asunto(s)
Diferenciación Celular , Ganglios Espinales/patología , Células-Madre Neurales/fisiología , Oligodendroglía/metabolismo , Polirradiculopatía/terapia , Animales , Cauda Equina/patología , Cauda Equina/fisiopatología , Células Cultivadas , Masculino , Regeneración Nerviosa , Células-Madre Neurales/trasplante , Nocicepción , Polirradiculopatía/fisiopatología , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Esferoides Celulares/metabolismoRESUMEN
We investigated a possible association of collagen IX tryptophan (Trp) alleles (Trp2 and Trp3) and smoking with cervical spondylotic myelopathy (CSM) in 172 Chinese patients and 176 age- and gender-matched controls. The smoking status was evaluated by smoking index (SI). The CSM cases had a significantly higher prevalence of Trp2 alleles (Trp2+) than controls (19.8 vs 6.2%, P = 0.002), but the prevalence of Trp3 alleles (Trp3+) was similar between the two groups (23.3 vs 21.6%, P = 0.713). Logistic regression analyses showed that the subjects with Trp2+ had a higher risk for CSM. We thus analyzed whether smoking status influenced the association between Trp2 alleles and CSM risk. Among Trp2+ subjects with an SI less than 100, the smoking status did not influence the effect of risk for SCM [odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 0.85-2.18, P > 0.05]. When SI increased from 101 to 300, the OR for CSM reached 3.34 (95%CI = 2.11-5.67, P = 0.011); when SI was more than 300, the OR for CSM reached 5.56 (95%CI = 3.62-7.36, P < 0.001). Among Trp2- subjects with SI more than 300, the OR for CSM increased 2.14 (95%CI = 1.15-4.07, P = 0.024). We found a significant association between the Trp2 alleles and CSM risk and smoking amplifies this risk, suggesting that smoking abstinence is important for reducing CSM occurrence in subjects with high genetic risk.