Genetic polymorphisms of nerve growth factor receptor (NGFR) and the risk of Alzheimer's disease

This was a case-control study in a Chinese population. A total of 264 AD patients were recruited from three teaching hospitals between 2007 to 2010; 389 controls were recruited from elderly health checkup and volunteers of the hospital during the same period of time. Five common (frequency≥5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from NGFR to test the association between NGFR htSNPs and the risk of AD.Variant NGFR rs734194 was significantly associated with a decreased risk of AD [GG vs. TT copies: adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.20-0.95]. Seven common haplotypes were identified. Minor haplotype GCGCG was significantly associated with a decreased risk of AD (2 vs. 0 copies: adjusted OR = 0.39, 95% CI = 0.17-0.91). Type 2 DM significantly modified the association between rs2072446, rs741072, and haplotype GCTTG and GTTCG on the risk of AD among ApoE ε4 non-carriers (Pinteraction < 0.05).Inherited polymorphisms of NGFR were associated with the risk of AD; results were not significant after correction for multiple tests. This association was further modified by the status of type 2 DM.Dementia is a degenerative brain syndrome characterized by decline or loss in cognitive function [1]. About 30 million elders suffered from dementia worldwide in 2008 estimated by Alzheimer's Disease International. Alzheimer's disease (AD) is the most common causes of dementia and was the fifth leading cause of death for those aged 65 or older in the United States in 2006 [1]. In Taiwan, more than 160,000 people were demented in 2009 [2] and the number of AD patients keeps raising in many aging populations.Degeneration of basal forebrain cholinergic neurons (BFCN) has shown to modulate cognitive function in AD patients [3,4]. Nerve growth factor receptor (NGFR, also called p75NTR) is one of the receptors of NGF and is expressed at the end of cholinergic axon [5,6]. The gene encoding NGFR is located on chromosome 17q21-q2