The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults

Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

Efectos del polimorfismo Val108/158Met del gen dopaminérgico Catecol-O-metiltransferasa COMT en las funciones ejecutivas de preescolares / Effects of dopamine gene polymorphism Val108/158Met Catechol-O-methyltransferase COMT in executive functions in preschool

El nivel de Dopamina en la Corteza Prefrontal se ha relacionado al desempeño de las Funciones Ejecutivas (FE). El objetivo de este estudio es explorar el efecto del polimorfismo funcional del gen COMT (Val/Val,Val/Met y Met/Met) en las FE de preescolares. Se utilizó la Batería Neuropsicológica de Funciones Ejecutivas para niños, y se extrajo el ADN genómico según metodología estándar (N=248) de 3 a 6 años de edad (M=4.6). Se estudiaron las frecuencias genotípicas del gen COMT y se realizó un análisis de varianza (ANOVA one-way) estableciendo diferencias significativas con una p<0.05. Los niños con el polimorfismo de baja actividad Met/Met puntúan significativamente mejor en relación a los niños con polimorfismo Val/Val en pruebas que requieren de Inhibición y los niños con el polimorfismo de alta actividad Val/Val resultan con un mejor rendimiento en pruebas relacionadas a MT, Planeación y Abstracción que los niños con polimorfismo Met/Met y Val/Met. Estos resultados parecen reflejar el papel de la enzima COMT como regulador de DA y que tanto el hipermetabolismo como el hipometabolismo tiene implicaciones importantes en las FE.

The level of DA in the prefrontal cortex has been related to the performance on executive functions (EF). The objective of this study was to explore the effect of the COMT polymorphism (Val/Val, Val/Met, Met/Met) in the performance of EF in a population of preschool children. All subjects were evaluated with a Neuropsychological Battery and genomic DNA was extracted according to standard methodology (N=248) from 3 to 6 years of age (M=4.6). We studied genotypic frequencies of the COMT gene and an analysis of variance (one-way ANOVA) with post hoc analysis, establishing significant differences at p<0.05. In Children with a low activity polymorphism Met/Met scored significantly better in relation to the children with polymorphism Val/Val in tests requiring inhibition and children with high activity polymorphism Val/Val had better performance on tests related to working memory, planning and abstraction that children with polymorphism Met/Met and Val/Met. These results seem to reflect the role of COMT enzyme as a regulator of DA and that both hypermetabolism and hypometabolism has important implications for the EF.

YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study

OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.

Fibrinogen Yecheon: Congenital Dysfibrinogenemia with Gamma Methionine-310 to Threonine Substitution

This case study reports a rare fibrinogen variant, gamma Met310Thr mutation, for the first time in Korea. The case shows a point mutation from T to C in the 1,007th nucleotide of the FGG gene. This report describes a variant fibrinogen, hereinafter called "fibrinogen Yecheon", using the name after the town where the patient was living at the time of diagnosis. Fibrinogen Yecheon has a de novo heterozygous point mutation of FGG resulting in gamma Met310Thr and subsequent extra N-glycosylation at gamma Asn308. Extra N-glycosylated fibrinogen is considered a main inhibitor of normal fibrinogen activity.

Controlling proteolytic degradation of the methionine enriched MB-1Trp protein

Protein design is currently used for the creation of new proteins with desirable traits, which include a superior nutritional value. One of the challenges of protein design in this area is to achieve the production of stable native-like proteins that resist the proteolytic pressure of the organism used for its production (the bioreactor). We report here the identification of a specific peptide bond sensitive to E. coli proteolysis in the designer protein MB-1Trp. In an attempt to reduce proteolysis, we have created a MB-1TrpHis gene library in which the two amino acids surrounding the peptide bond, N44 and L45, were randomized using degenerated oligonucleotides. The initial characterization of MB-1TrpHis N44E/L45V and MB-1TrpHis N44E/L45M, 2 variants of the library that were more resistant than the parent protein, was performed in order to investigate the nature of the mutants' resistance. Our results suggest that the mutants behaved like MB-1Trp regarding folding and thermal stability, and that proteolytic resistance is due to the elimination of the protease recognition site.