APOLIPOPROTEIN-E GENOTYPE OF A PORTUGUESE CONTROL POPULATION AND ALZHEIMERS-DISEASE PATIENTS

The present work first describes the frequency of APOE alleles and gen otypes in Portuguese populations in relation to AD pathology. We genot yped a group of late onset sporadic AD cases, their pairwise controls and a larger group of randomly selected individuals, to assess the dis tribution pattern of APOE alleles in the Portuguese population, APOE e psilon 4 relative frequency may significantly vary among different pop ulations-a fact which should be taken into consideration for the corre ct evaluation of the cossegregation of this allele with AD pathology, We observed a frequency of 0.087 +/- 0.029 of the APOE epsilon 4 and 0 .043 +/- 0.021 of the APOE epsilon 2 allele in the Portuguese random p opulation which as expected showed a marked prevalence of the APOE eps ilon 3 form (0.870 +/- 0.035). In the AD patients the APOE epsilon 4 a llele frequency was significantly higher (0.360 +/- 0.081) than in the controls (chi(2) = 31.000, p < 0.00001, df = 2). Consistently APOE ep silon 3 allele frequency (0.640 +/- 0.081) was significantly lower tha n in the controls while APOE epsilon 2 was absent in the studied AD po pulation. Taken together our results demonstrate that the Portuguese p opulation is characterized by a relatively low frequency of the APOE e psilon 4 allele, in good agreement with previous observations of a gra dient of epsilon 4 allele frequency in Europe, decreasing from North t o South. Several lines of evidence point at APOE epsilon e4 allele as a major genetic susceptibility factor in AD. The APOE epsilon 4 allele was significantly higher [odds ratio (OR) = 5.93, 95% CI 3.55-9.91] i n the Portuguese AD patients than in the random non-demented populatio n, The genotype analysis of the Portuguese AD patients here described reveals a marked, increased frequency of epsilon 4 homo- and heterozyg ous individuals consistent with an APOE epsilon 4 zigosity effect as a further genetic trait predisposing to AD development.