Gene polymorphism in apolipoprotein E and presenilin-1 in patients with late-onset Alzheimer's disease

Objective To evaluate the association of apolipoprotein E (apoE) and presenilin-1 (PS-I) gene polymorphism with late-onset Alzheimer's disease (AD), Methods A case-control study was undertaken to detect the polymorphism of apoE 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 in late-onset AD (n = 42) were significantly higher than those of age-matched 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 than 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 risk for late-onset AD compared with that with no epsilon 4 allele (odds ratio: 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 significant (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 apoE 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 genotype 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.