Tp. Cui et al., Gene polymorphism in apolipoprotein E and presenilin-1 in patients with late-onset Alzheimer's disease, CHIN MED J, 113(4), 2000, pp. 340-344
Objective To evaluate the association of apolipoprotein E (apoE) and presen
ilin-1 (PS-I) gene polymorphism with late-onset Alzheimer's disease (AD),
Methods A case-control study was undertaken to detect the polymorphism of a
poE and PS-1 by polymerase chain reaction and digestion with endonucleases
of BspL I, Hha I and BamH I.
Results The frequencies of apoE epsilon 3/4 genotype and epsilon 4 allele i
n late-onset AD (n = 42) were significantly higher than those of age-matche
d controls (P < 0.05). The frequencies of the apoE intron 1 enhancer (IE1)
G/G genotype and G allele in late-onset AD were also significantly higher t
han those in controls (P < 0.05). The frequencies of the PS-1 1/1 genotype
but not the 1 allele in AD were significantly higher than those in controls
(P < 0.05). The apoE epsilon 4 allele was associated with a tripling of ri
sk for late-onset AD compared with that with no epsilon 4 allele (odds rati
o: 2.932). Homozygosity of the G allele in IE1 and 1/1 genotype in PS-I was
associated with a doubling of risk for late-onset AD, and odds ratios were
2.223 and 2.066, respectively. When the apoE epsilon 4 was controlled, the
association between the IE1 G/G genotype AD was no longer statistically si
gnificant (P > 0.05). We sequenced the exon 4 of apoE in patients with late
-onset AD, and found no other genetic polymorphism or mutation except for a
poE epsilon 4 and IE1 G alleles associated with AD,
Conclusion apoE epsilon 4 gene appears to be the strongest gene risk factor
for late-onset AD and its apparent association between the IE1 G/G genotyp
e and late-onset AD is a consequence of the association between the epsilon
4 and IE1 G/G genotype. The PS-1/1 genotype is weakly associated with late
-onset AD.