GenotypePhenotype correlations

1
Genotype-Phenotype correlations

• ApoE a Frailty gene?

ECHA Project Steering committe
Arcavacata di Rende 17 January 2004
Valentina Greco
2
Is ApoE a Longevity gene?

• ApoE-e4 allele decrases and ApoE-e2 increases in
  centenarians with respect to young controls
  (confirmed in different population)

However, no excess of e4 allele sharing in aged
siblings (Nemani et al2000)
3
WHY?
Low statistical power of non-parametric linkage
analysis
Is ApoE a frailty gene?
4
ApoE a Frailty gene

• ApoE-e4 allele is a risk factor for dementia and
  late-onset AD

Does the ApoE-e4 allele function as a risk factor
for cognitive impairment in normal aging?
5
ApoE-MMSE

• We correlate the association between cognitive
  function (MMSE) and ApoE variability in the Ist
  ECHA Generation

6
ApoE-MMSE

• MAIN PROBLEM

to evaluate MMSE scores in oldest people
7
(No Transcript)
8
MMSE scores distribution in the 1st Generation
9
Mann-Whitney Test
p0,112
MMSE scores as a function of ApoE genotype in
Generation 1
10
Mann-Whitney Test
p0,807
MMSE scores as a function of ApoE genotype in
Generation 2
11
FUTURE DIRECTIONS
The frequency distribution of mtDNA haplogroups
is different between e4carriers and non-carriers
in a sample of AD patients
Some mtDNA haplogroups (K and U) seem to
neutralize the harmful effect of the APO e4
allele (Carrieri et al2001)
mtDNA
APOE
MMSE
12
(No Transcript)