Genetic polymorphisms of nerve growth factor receptor (NGFR) and the risk of Alzheimer's disease
1 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
2 Department of Neurology, En Chu Kong Hospital, New Taipei City, Taiwan
3 Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
4 Research Center for Genes, Environment and Human Health, Taipei, Taiwan
5 Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan
6 Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan
7 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
8 Department of Laboratory Medicine, En Chu Kong Hospital, New Taipei City, Taiwan
9 Center of Neurological Medicine, Cardinal Tien's Hospital, New Taipei City, Taiwan
10 Department of Laboratory Medicine, Cardinal Tien's Hospital, New Taipei City, Taiwan
Journal of Negative Results in BioMedicine 2012, 11:5 doi:10.1186/1477-5751-11-5Published: 12 January 2012
Loss of basal forebrain cholinergic neurons is attributable to the proapoptotic signaling induced by nerve growth factor receptor (NGFR) and may link to Alzheimer's disease (AD) risk. Only one study has investigated the association between NGFR polymorphisms and the risk of AD in an Italian population. Type 2 diabetes mellitus (DM) may modify this association based on previous animal and epidemiologic studies.
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.