SNPs in Neurotrophin System Genes and Alzheimer's Disease in an Italian Population

Abstract

Increasing evidence suggests a role for nerve growth factor (NGFB), brain-derived neurotrophic factor (BDNF), and their receptors, nerve growth factor receptor (NGFR), and neurotrophin tyrosine kinase receptors 1 and 2 (NTRK1 and NTRK2), in Alzheimer's disease (AD). However, genetic association between the neurotrophin system genes and AD has been poorly investigated. We genotyped 21 single nucleotide polymorphisms (SNPs) within these genes in a population of Italian AD patients and healthy controls. We found an allele-wise association of rs2072446 on NGFR with familial AD (fAD, p = 0.047), and a genotype-wise association of rs2289656 on NTRK2 with sporadic AD (sAD, p = 0.0036). rs6336 on NTRK1 resulted associated to early-onset sAD in both allele-wise (p = 0.028) and genotype-wise (p = 0.014) analysis, while rs1048218 on BDNF showed allele-wise association with late-onset sAD (p = 0.047). A trend to association with sAD and/or fAD was observed for other SNPs. Our results suggest that genetic variants of neurotrophin system genes might confer susceptibility to AD.

Association of BDNF and BCHE with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls

“…Heterozygous carriers of the T-allele tend to have a higher risk of developing AD than non-carriers (36). There have been a total of four significant results (13,(17)(18)(19)) and 14 non-significant results (28)(29)(30)(31)(34)(35)(36)(37)40,41,(43)(44)(45) among the previous association studies between the BDNF C270T polymorphism and AD. In the present meta-analysis, the BDNF C270T polymorphism was found to increase the risk of AD by 88% in Asians under the dominant model.…”

“…Previous studies have reported five positive results (12-16) and 21 negative results (19,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) between the BDNF Val66Met polymorphism and AD. In the present meta-analysis, no significant association was found between BDNF Val66Met and AD (P>0.05, Table II).…”

“…For BDNF Val66Met, there have been five positive results in Europeans (12)(13)(14)(15) and Asians (16), and 21 negative results (among 18 studies) in Europeans (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37), Asians (19,(38)(39)(40)(41)(42) and Africans (29). For BDNF C270T, there have been four positive results in Europeans (13,17) and Asians (18,19) and 14 negative results in Europeans (28)(29)(30)(31)(34)(35)(36)(37)(43)(44)(45), Asians (40,41) and Africans (29). For BCHE-K variants, there have been six positive results in Europeans (46-51) and 22 negative results in Europeans (5,(52)(53)(54)(55)…”

A novel hypothesis for Alzheimer disease based on neuronal tetraploidy induced by p75NTR

“…89,90 Finally, p75 NTR has also been shown to physically and functionally interact with APP, 91 and a direct genetic link between p75 NTR and AD has been suggested. 92 …”

Association of Brain-Derived Neurotrophic Factor (BDNF) Gene Snps G196A and C270T with Alzheimer’s Disease: A Meta-Analysis

“…Detailed characteristics of all eligible studies included in meta-analysis are reported in Table 1. One overall study was conducted on BDNF 196GA polymorphism and 3 ethnicity specific studies were conducted, that includes 8 studies on American populations [30][31][32][33][34][35][36], 11 studies on Asian populations [37][38][39][40][41][42][43][44][45][46][47] and 12 studies on European populations [35,[48][49][50][51][52][53][54][55][56][57][58]. Moreover, one overall study was also conducted on BDNF 270CT polymorphism and 3 ethnicity specific studies were also possible, that includes 5 studies on American populations [30,31,33,34,59], 7 studies on Asian populations [37,39,41,42,44,46,60] and 7 studies on European populations [48,49,52,…”