No genetic association between ATP binding cassette proteins and Japanese sporadic Alzheimer's disease.
The identification of the epsilon4 variant of apolipoprotein E as a genetic risk factor for late-onset Alzheimer's disease (AD) suggests that cholesterol may play a direct role in the pathogenesis of the disease. Recent studies have suggested that the ATP-binding cassette (ABC) protein G5 (ABCG5) may be involved in the regulation of intestinal cholesterol absorption. Furthermore, genetic variation of this locus may affect blood cholesterol concentrations. We therefore studied whether the ABCG5 C1950G (Gln640Glu) polymorphism affects the risk of AD. In addition, there was no difference in mean baseline cholesterol concentrations between individuals with the C/C genotype and carriers of the G allele. Recent studies have shown that genetic regions including the ABCA12 gene might also be associated with the risk of AD. The ABCA12 gene, located <1 Mb from the peak marker on chromosome 2q34, is also a member of the ABC transporter superfamily. In the current study, two common polymorphisms of the ABCA12 gene, rs952718 (T/G) and rs956133 (A/G), were analyzed in our subjects. These polymorphisms showed no association with the risk of AD. Furthermore, we observed weak linkage disequilibrium between these two single nucleotide polymorphisms. These results indicate that the common polymorphisms of the ABCG5 and ABCA12 genes investigated here are not associated with AD.
Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan. taku1974@med.juntendo.ac.jp
Taku
T
Ohkubo
Nobuto
N
Shibata
Tohru
T
Ohnuma
Shinji
S
Higashi
Chie
C
Usui
Akira
A
Ueki
Masatsugu
M
Nagao
Heii
H
Arai
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008074:Lipoproteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
C473801:ABCA12 protein, human; C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D008074:Lipoproteins; D004247:DNA