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意大利人群中神经营养因子系统基因单核苷酸多态性与阿尔茨海默病

SNPs in neurotrophin system genes and Alzheimer's disease in an Italian population.

作者信息

Cozza Arianna, Melissari Erika, Iacopetti Paola, Mariotti Veronica, Tedde Andrea, Nacmias Benedetta, Conte Angela, Sorbi Sandro, Pellegrini Silvia

机构信息

Department of Experimental Pathology, Medical Biotechnology, Infectious Diseases and Epidemiology, University of Pisa, Pisa, Italy.

出版信息

J Alzheimers Dis. 2008 Sep;15(1):61-70. doi: 10.3233/jad-2008-15105.

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.

摘要

越来越多的证据表明,神经生长因子(NGFB)、脑源性神经营养因子(BDNF)及其受体神经生长因子受体(NGFR)和神经营养酪氨酸激酶受体1和2(NTRK1和NTRK2)在阿尔茨海默病(AD)中发挥作用。然而,神经营养因子系统基因与AD之间的遗传关联研究较少。我们对一组意大利AD患者和健康对照者的这些基因中的21个单核苷酸多态性(SNP)进行了基因分型。我们发现NGFR上的rs2072446与家族性AD(fAD,p = 0.047)存在等位基因关联,NTRK2上的rs2289656与散发性AD(sAD,p = 0.0036)存在基因型关联。在等位基因分析(p = 0.028)和基因型分析(p = 0.014)中,NTRK1上的rs6336均与早发性sAD相关,而BDNF上的rs1048218与晚发性sAD存在等位基因关联(p = 0.047)。其他SNP观察到与sAD和/或fAD的关联趋势。我们的结果表明,神经营养因子系统基因的遗传变异可能使个体易患AD。

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