No association between the brain-derived neurotrophic factor 196 G>A or 270 C>T polymorphisms and Alzheimer's or Parkinson's disease.
ABSTRACT 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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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.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2009; 153B(1):235-42. DOI:10.1002/ajmg.b.30986 · 3.27 Impact Factor
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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.Journal of Neurochemistry 05/2008; 105(1):1-17. DOI:10.1111/j.1471-4159.2008.05237.x · 4.24 Impact Factor
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ABSTRACT: Both of environmental and genetic factors confer vulnerability to Parkinson's disease (PD). NR4A2 (Nurr1), a member of the steroid/thyroid hormone nuclear receptor superfamily, is essential for the neurogenesis and differentiation of dopaminergic neurons in the midbrain. Brain derived neurotrophic factor (BDNF) deficiency may play a role in the pathogenesis of PD, as the surviving dopaminergic nigrostriatal neurons have reduced levels of BDNF. This study examines whether BDNF V66M (c.196 G --> A) or NR4A2 IVS6 +18insG polymorphism is associated with the risk of Taiwanese PD and the age of onset using a case-control study. The genotype or allele frequency distribution of both BDNF V66M and NR4A2 IVS6 +18insG polymorphisms was not significantly different between the cases and the controls. Neither BDNF nor NR4A2 polymorphism influences PD onset age. Notably, after stratification by sex, female individuals carrying the NR4A2 2G/2G genotype demonstrated a trend toward significant decrease in risk of developing PD (OR = 0.49, 95% CI = 0.25-0.96, P = 0.039). These results suggest that the NR4A2 IVS6 +18insG polymorphism may play a minor role in PD susceptibility among Taiwanese women.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 06/2007; 144B(4):458-62. DOI:10.1002/ajmg.b.30476 · 3.27 Impact Factor