PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-6 (6)
 

Clipboard (0)
None
Journals
Authors
more »
Year of Publication
Document Types
1.  Genomic NGFB variation and multiple sclerosis in a case control study 
BMC Medical Genetics  2008;9:107.
Background
Nerve growth factor β (NGFB) is involved in cell proliferation and survival, and it is a mediator of the immune response. ProNGF, the precursor protein of NGFB, has been shown to induce cell death via interaction with the p75 neurotrophin receptor. In addition, this neurotrophin is differentially expressed in males and females. Hence NGFB is a good candidate to influence the course of multiple sclerosis (MS), much like in the murine model of experimental autoimmune encephalomyelitis (EAE).
Methods
Ten single nucleotide polymorphisms (SNPs) were genotyped in the NGFB gene in up to 1120 unrelated MS patients and 869 controls. Expression analyses were performed for selected MS patients in order to elucidate the possible functional relevance of the SNPs.
Results
Significant association of NGFB variations with MS is evident for two SNPs. NGFB mRNA seems to be expressed in sex- and disease progression-related manner in peripheral blood mononuclear cells.
Conclusion
NGFB variation and expression levels appear as modulating factors in the development of MS.
doi:10.1186/1471-2350-9-107
PMCID: PMC2613874  PMID: 19063739
2.  No association between polymorphisms in the BDNF gene and age at onset in Huntington disease 
BMC Medical Genetics  2006;7:79.
Background
Recent evidence suggests that brain-derived neurotrophic factor (BDNF) is an attractive candidate for modifying age at onset (AO) in Huntington disease (HD). In particular, the functional Val66Met polymorphism appeared to exert a significant effect. Here we evaluate BDNF variability with respect to AO of HD using markers that represent the entire locus.
Methods
Five selected tagging polymorphisms were genotyped across a 65 kb region comprising the BDNF gene in a well established cohort of 250 unrelated German HD patients.
Results
Addition of BDNF genotype variations or one of the marker haplotypes to the effect of CAG repeat lengths did not affect the variance of the AO.
Conclusion
We were unable to verify a recently reported association between the functional Val66Met polymorphism in the BDNF gene and AO in HD. From our findings, we conclude that neither sequence variations in nor near the gene contribute significantly to the variance of AO.
doi:10.1186/1471-2350-7-79
PMCID: PMC1637098  PMID: 17096834
3.  Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene (MFN2) 
BMC Medical Genetics  2006;7:53.
Background
Charcot-Marie-Tooth neuropathies are a group of genetically heterogeneous diseases of the peripheral nervous system. Mutations in the MFN2 gene have been reported as the primary cause of Charcot-Marie-Tooth disease type 2A.
Methods
Patients with the clinical diagnosis of Charcot-Marie-Tooth type 2 were screened using single strand conformation polymorphism (SSCP). All DNA samples showing band shifts in the SSCP analysis were amplified from genomic DNA and cycle sequenced.
Results
We analyzed a total of 73 unrelated patients with a clinical diagnosis of CMT 2. Overall, novel mutations were detected in 6 patients. c.380G>T (G127V), c.1128G>A (M376I), c.1040A>T (E347V), c.1403G>A (R468H), c.2113G>A (V705I), and c.2258_2259insT (L753fs).
Conclusion
We confirmed a significant role of mutations in MFN2 in the pathogenesis of Charcot-Marie-Tooth disease type 2.
doi:10.1186/1471-2350-7-53
PMCID: PMC1524942  PMID: 16762064
4.  Age at onset of Huntington disease is not modulated by the R72P variation in TP53 and the R196K variation in the gene coding for the human caspase activated DNase (hCAD) 
BMC Medical Genetics  2005;6:35.
Background
TP53 is an attractive candidate for modifying age of onset (AO) in Huntington disease (HD): The amino-terminus of the mutated huntingtin (htt) exon 1 translation product has functional properties which may affect critically the TP53 pathway in HD neurons. The pathogenic domain of mutant htt interacts with nuclear transcription factors, and it potentially modulates TP53-induced transcriptional events. A single nucleotide polymorphism (SNP) resulting in the R72P exchange in TP53 protein might modulate the variation in AO. In addition, also the R196K replacement in human caspase activated DNase (hCAD) may theoretically affect the AO.
Methods
We have genotyped the polymorphisms R72P and R196K in a well established cohort of 167 unrelated HD patients.
Results
The expanded CAG repeat explained 30.8% of the variance in AO. Adding the genotypes of the SNPs investigated did not affect the variance of the AO variance explained.
Conclusion
In this replication study, no association was found explaining a significant amount of the variability in AO of HD thus contradicting a recent report.
doi:10.1186/1471-2350-6-35
PMCID: PMC1253512  PMID: 16202123
5.  Evaluation of the toll-like receptor 6 Ser249Pro polymorphism in patients with asthma, atopic dermatitis and chronic obstructive pulmonary disease 
BMC Medical Genetics  2005;6:34.
Background
For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis'). Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases. We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD).
Methods
Genotyping of the Ser249Pro polymorphism in 68 unrelated adult patients and 132 unrelated children with asthma, 185 unrelated patients with COPD, 295 unrelated individuals with AD and 212 healthy control subjects was performed by restriction enzyme digestion.
Results
We found a weak association of the 249Ser allele with childhood asthma (p = 0.03). Yet, significance was lost after Bonferroni correction. No association was evident for AD or COPD.
Conclusion
Variation in TLR6 might play a role in the pathogenesis of childhood asthma.
doi:10.1186/1471-2350-6-34
PMCID: PMC1262722  PMID: 16188043
6.  Glutathione S-Transferase Ω 1 variation does not influence age at onset of Huntington's disease 
Background
Huntington's disease (HD) is a fully penetrant, autosomal dominantly inherited disorder associated with abnormal expansions of a stretch of perfect CAG repeats in the 5' part of the IT15 gene. The number of repeat units is highly predictive for the age at onset (AO) of the disorder. But AO is only modestly correlated with repeat length when intermediate HD expansions are considered. Circumstantial evidence suggests that additional features of the HD course are based on genetic traits. Therefore, it may be possible to investigate the genetic background of HD, i.e. to map the loci underlying the development and progression of the disease. Recently an association of Glutathione S-Transferase Ω 1 (GSTO1) and possibly of GSTO2 with AO was demonstrated for, both, Alzheimer's (AD) and Parkinson's disease (PD).
Methods
We have genotyped the polymorphisms rs4925 GSTO1 and rs2297235 GSTO2 in 232 patients with HD and 228 controls.
Results
After genotyping GSTO1 and GSTO2 polymorphisms, firstly there was no statistically significant difference in AO for HD patients, as well as secondly for HD patients vs. controls concerning, both, genotype and allele frequencies, respectively.
Conclusion
The GSTO1 and GSTO2 genes flanked by the investigated polymorphisms are not comprised in a primary candidate region influencing AO in HD.
doi:10.1186/1471-2350-5-7
PMCID: PMC394327  PMID: 15040808

Results 1-6 (6)