No association between the brain-derived neurotrophic factor 196G>A or 270C>T polymorphisms and Alzheimer’s or Parkinson’s disease. Folia Neuropathol

Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Center for Laboratory Medicine, Tampere University, Tampere, Finland.
Folia Neuropathologica (Impact Factor: 1.57). 01/2006; 44(1):12-6.
Source: PubMed


The brain-derived neurotrophic factor (BDNF) promotes survival, differentiation and maintenance of neurons in the central nervous system. BDNF 196 G>A and 270 C>T polymorphisms have previously been associated with Alzheimer's disease (AD) and with Parkinson's disease (PD). To study the role of BDNF 196 G>A and 270 C>T polymorphisms in Finnish AD and PD patients we genotyped BDNF 196 G>A and 270 C>T polymorphisms in 97 sporadic AD patients, 52 PD patients and 101 control subjects with polymerase chain reaction. No associations were found between the genotypes studied and AD or PD in Finnish patients. Moreover, no interaction between either BDNF polymorphism and the epsilon 4 allele of apolipoprotein E was found. In conclusion, it seems that the BDNF gene does not contribute significantly to the risk of AD or PD in Finnish patients.

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    • "Although a polymorphism in the apolipoprotein E (ApoE) gene has been found to be associated with familial AD, it might not provide a sensitivity or high-enough specificity to be used alone as a diagnostic test for the disease [7]. "
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    ABSTRACT: Objective: We evaluated whether the methylenetetrahydrofolate reductase (MTHFR) 677C>T marker influences the risk and severity of Alzheimer's disease (AD) and whether AD is associated with homocysteine, vitamin B12, and cholesterol levels in Egypt. Methods: Forty-three Alzheimer's cases and 32 non-AD controls were genotyped for the 677C>T polymorphism. Clinical characteristics and levels of homocysteine, vitamin B12, and cholesterol were assessed. Results: No significant differences in the frequencies of the MTHFR alleles or genotypes between AD cases and controls (P = 0.14) were identified. The 677T mutant allele was significantly overrepresented in AD cases compared to controls (OR = 2.22; P = 0.03). The 677T/T frequency was three times higher in AD patients than in controls, which could increase plasma homocysteine levels. Severe cases of AD were the most frequent in patients with the T/T genotype (11.6%). The effect of the MTHFR polymorphism on the risk of AD may be independent of homocysteine, vitamin B12, or even cholesterol levels. Conclusions: The MTHFR 677C>T polymorphism--especially the presence of one copy of the T allele--appears to confer a potential risk for the development of AD. The T/T genotype may contribute to hypercysteinemia as a sensitive marker.
    Full-text · Article · Sep 2013 · Disease markers
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    • "Subsequently, two other groups reported that the T270 allele was significantly associated with an increased risk of AD [Nishimura et al., 2004; Olin et al., 2005], while one group reported the opposite [Saarela et al., 2006]. Other studies reported no significant association (Supplementary Fig. 2) [Riemenschneider et al., 2002; Bagnoli et al., 2004; Nishimura et al., 2004; Bodner et al., 2005; Desai et al., 2005; Lee et al., 2005; Matsushita et al., 2005; Akatsu et al., 2006; Tsai et al., 2006; Zhang et al., 2006; Huang et al., 2007]. "
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    ABSTRACT: Conflicting results have been reported as to whether genetic variations (Val66Met and C270T) of the brain-derived neurotrophic factor gene (BDNF) confer susceptibility to Alzheimer's disease (AD). We genotyped these polymorphisms in a Japanese sample of 657 patients with AD and 525 controls, and obtained weak evidence of association for Val66Met (P = 0.063), but not for C270T. After stratification by sex, we found a significant allelic association between Val66Met and AD in women (P = 0.017), but not in men. To confirm these observations, we collected genotyping data for each sex from 16 research centers worldwide (4,711 patients and 4,537 controls in total). The meta-analysis revealed that there was a clear sex difference in the allelic association; the Met66 allele confers susceptibility to AD in women (odds ratio = 1.14, 95% CI 1.05-1.24, P = 0.002), but not in men. Our results provide evidence that the Met66 allele of BDNF has a sexually dimorphic effect on susceptibility to AD.
    Full-text · Article · Jan 2009 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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    • "Results have produced contradictory findings. Two studies indicate that homozygosity for the Val66Met polymorphism is associated with PD (Toda et al. 2003; Karamohamed et al. 2005), while others in the literature report no association (Hakansson et al. 2003; Hong et al. 2003; Saarela et al. 2006). Genetic linkage studies also show no evidence for BDNF as a candidate gene in familial PD (Gasser et al. 1994; Wirdefeldt et al. 2003). "
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    ABSTRACT: It is clear that brain-derived neurotrophic factor (BDNF) plays a crucial role in organizing the response of the genome to dynamic changes in the extracellular environment that enable brain plasticity. BDNF has emerged as one of the most important signaling molecules for the developing nervous system as well as the impaired nervous system, and multiple diseases, such as Alzheimer's, Parkinson's, Huntington's, epilepsy, Rett's syndrome, and psychiatric depression, are linked by their association with potential dysregulation of BDNF-driven signal transduction programs. These programs are responsible for controlling the amount of activated transcription factors, such as cAMP response element binding protein, that coordinate the expression of multiple brain proteins, like ion channels and early growth response factors, whose job is to maintain the balance of excitation and inhibition in the nervous system. In this review, we will explore the evidence for BDNF's role in gene regulation side by side with its potential role in the etiology of neurological diseases. It is hoped that by bringing the datasets together in these diverse fields we can help develop the foundation for future studies aimed at understanding basic principles of gene regulation in the nervous system and how they can be harnessed to develop new therapeutic opportunities.
    Preview · Article · May 2008 · Journal of Neurochemistry
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