Premium
[P3–109]: ALLELIC DISTRIBUTION OF GENES FOR APOLIPOPROTEIN E AND MTHFR IN PATIENTS WITH ALZHEIMER's DISEASE AND THEIR EPISTATIC INTERACTION
Author(s) -
Sutovsky Stanislav,
Petrovic Robert,
Turcani Peter
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.1320
Subject(s) - methylenetetrahydrofolate reductase , apolipoprotein e , epistasis , genotype , allele , odds ratio , medicine , gastroenterology , polymorphism (computer science) , genetics , disease , gene , biology
APOEε3 and APOEε4 whereof the latter increases the risk of disease 4-15 fold in a dose-dependent manner whilst APOEε2 appears to be protective. The biological mechanisms underlying the modified risk of disease in APOEε2 and APOEε4 carriers are not known. We previously showed that APOEε4carriers exhibit a prominent plasma apolipoprotein E (apoE) deficiency caused by a specific reduction of the apoE4 isoform. This apoE deficiency was not observed in cerebrospinal fluid. In cognitively intact APOEε3/ε4 carriers an increased relative ratio of plasma apoE4 to apoE3 correlated to glucose hypometabolism and gray matter volume reductions in brain areas most often affected in AD. Hence, we speculate that peripheral apoE levels are linked to processes driving the risk of developing AD brain pathology. In order to determine the cause of the observed phenotype of plasma apoE deficiency in APOEε4-carriers we aimed to investigate the expression of different APOE alleles in liver biopsies from individuals with an APOEε3/ε4 versus an APOEε2/ε3 genotype. Methods: Liver biopsies from liver explants were received from n1⁄43 APOEε3/ε4 and n1⁄43 APOEε2/ε3 carriers who had undergone liver transplantation at the Karolinska University Hospital in Sweden. Total RNA ( 80% in DV200 score) was isolated according to routine laboratory methods and used for RNA sequencing employing the high-throughput Illumina platform. Paired-end sequencing reads were aligned to the human reference genome (hg19), using TopHat, and gene counts for expression determined using HTseq-count. Differential expression between the genotype groups was calculated using DEseq2. Results: Preliminary analyses revealed differential expression of n1⁄4624 genes between individuals with an APOEε3/ε4 versus an APOEε2/ε3 genotype. Conclusions: In total n1⁄4624 genes are differentially expressed in livers from APOEε3/ε4 versus APOEε2/ε3 carriers. Further analyses will reveal the identity of the differentially expressed genes and whether there is a specific difference in the expression of APOE alleles that could explain the observed APOEε4 related plasma apoE deficiency