Risk of Alzheimer's disease is associated with a very low-density lipoprotein receptor genotype in Northern Ireland.
The epsilon-4 allele of apolipoprotein E (APOE) is associated with increased risk of Alzheimer's disease (AD), but the pathogenic mechanism is unknown. The 5-repeat allele of a CGG repeat polymorphism in the 5' untranslated region of the very low-density lipoprotein receptor (VLDL-R) gene, a receptor for apoE, has been found to be associated with increased risk of AD in a Japanese population. Other groups have been unable to replicate this in American Caucasian populations. A case-control study utilizing a clinically well-defined group of late-onset AD patients (n = 108) and age- and sex-matched control subjects (n = 108) from Northern Ireland was performed to test this association in a relatively homogeneous population. The 9,9 genotype of the VLDL-R was found to be significantly increased in patients compared to controls (P = 0.003; Pcorr = 0.035), leading to an increased risk of AD to subjects with this genotype (OR = 3.9; 95% CI, 1.52-11.25). In contrast to results from the Japanese study, the 5-repeat allele was found to be significantly reduced in the patient group when compared to controls (P = 0.008; Pcorr = 0.047). The results from this study suggest that individuals who have the 9,9 genotype of the VLDL-R gene are at increased risk of AD in Northern Ireland.
McIlroy
S P
SP
Department of Geriatric Medicine, Queen's University of Belfast, Northern Ireland. s.mcilroy@qub.ac.uk
Vahidassr
M D
MD
Savage
D A
DA
Patterson
C C
CC
Lawson
J T
JT
Passmore
A P
AP
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009660:Northern Ireland; D011973:Receptors, LDL / Q000235:genetics*; D012306:Risk; D018911:Trinucleotide Repeats
D001057:Apolipoproteins E; D011973:Receptors, LDL; C036053:VLDL receptor