INTRODUCTION: The apolipoprotein E (APOE) ε2 and ε4 alleles have beneficial and adverse impacts on Alzheimer's disease (AD), respectively, with incomplete penetrance, which may be modulated by other genetic variants. METHODS: We examined whether the associations of the APOE alleles with other polymorphisms in the genome can be sensitive to AD-affection status. RESULTS: We identified associations of the ε2 and ε4 alleles with 314 and 232 polymorphisms, respectively. Of them, 35 and 31 polymorphisms had significantly different effects in AD-affected and -unaffected groups, suggesting their potential involvement in the AD pathogenesis by modulating the effects of the ε2 and ε4 alleles, respectively. Our survival-type analysis of the AD risk supported modulating roles of multiple group-specific polymorphisms. Our functional analysis identified gene enrichment in multiple immune-related biological processes, for example, B cell function. DISCUSSION: These findings suggest involvement of local and inter-chromosomal modulators of the effects of the APOE alleles on the AD risk.
INTRODUCTION: The apolipoprotein E (APOE) ε2 and ε4 alleles have beneficial and adverse impacts on Alzheimer's disease (AD), respectively, with incomplete penetrance, which may be modulated by other genetic variants. METHODS: We examined whether the associations of the APOE alleles with other polymorphisms in the genome can be sensitive to AD-affection status. RESULTS: We identified associations of the ε2 and ε4 alleles with 314 and 232 polymorphisms, respectively. Of them, 35 and 31 polymorphisms had significantly different effects in AD-affected and -unaffected groups, suggesting their potential involvement in the AD pathogenesis by modulating the effects of the ε2 and ε4 alleles, respectively. Our survival-type analysis of the AD risk supported modulating roles of multiple group-specific polymorphisms. Our functional analysis identified gene enrichment in multiple immune-related biological processes, for example, B cell function. DISCUSSION: These findings suggest involvement of local and inter-chromosomal modulators of the effects of the APOE alleles on the AD risk.
Authors: Anna M Bennet; Emanuele Di Angelantonio; Zheng Ye; Frances Wensley; Anette Dahlin; Anders Ahlbom; Bernard Keavney; Rory Collins; Björn Wiman; Ulf de Faire; John Danesh Journal: JAMA Date: 2007-09-19 Impact factor: 56.272
Authors: Marthe T Maehlen; Sella A Provan; Diederik P C de Rooy; Annette H M van der Helm-van Mil; Annemarie Krabben; Tore Saxne; Elisabet Lindqvist; Anne Grete Semb; Till Uhlig; Désirée van der Heijde; Inger Lise Mero; Inge C Olsen; Tore K Kvien; Benedicte A Lie Journal: PLoS One Date: 2013-04-17 Impact factor: 3.240
Authors: Vladimir N Babenko; Dmitry A Afonnikov; Elena V Ignatieva; Anton V Klimov; Fedor E Gusev; Evgeny I Rogaev Journal: BMC Neurosci Date: 2018-04-19 Impact factor: 3.288