3.1. Apo E and apo C-I

The apo E allele distributions of the young popula- tion were not significantly different from either the total elderly population or the elderly men or women (Table 1). Analysis of apo E genotypes was restricted to E3:3, E 3:4 and E2:3, since the other genotypes were too rare to allow expected values of 5 or more in the (cid:120)2 contin- gency tables (Table 1). No significant difference was found when the total elderly sample or the elderly men were compared to the young sample. However, the genotype frequencies of the elderly women were differ- ent to those of the young sample ((cid:120)2(cid:30)7.49, 2 d.f., PB 0.05). Since apo E allele frequencies were no differ- ent in the elderly women compared to the young sam- ple, we also derived genotype frequencies in the young group from their allele frequencies on the basis of expectations according to Hardy-Weinberg equilibrium. This procedure was used under the assumption that no selection for apo E had occurred in the young group and that the genotype frequencies derived from the allele frequencies in the young group may be more representative than the observed genotypes, in view of the random variation of six genotypes which would be expected to occur in a sample of 200. These genotype frequencies were not significantly different to the ob- served genotypes in the elderly women.

Genotype

Apo E, apo C-I, ACE and MTHFR genotypes were determined as described by Hixson and Vernier [14], Nillesen et al. [15], Rigat et al. [16] and Frosst et al. [17], respectively. Observed allele and genotype frequen- cies were compared in the different groups using (cid:120)2 tests. Differences in genotype frequencies between groups were also analysed by a likelihood ratio test, in which the genotype frequencies in the young were con- strained to be in Hardy-Weinberg equilibrium and com- pared to the observed allele frequencies in the elderly men and women. Relative risks (odds ratios) and confi- dence limits for each of the polymorphisms were calcu- lated using standard methods [18].

Since apo C-I and apo E are less than 10 kb apart, apo C-I genotype and allele frequencies can be used to

  

3. Results

Age and sex distributions of the elderly men and women are shown in Fig. 1. Allele and genotype fre- quencies were determined for polymorphic loci associ- ated with each candidate gene and the following comparisons were made: the entire elderly group versus the entire young group, the elderly men versus the entire young group, the elderly women versus the entire young group and the elderly women versus the elderly men. For these autosomal genes, there is no reason to expect different genotype frequencies in young boys

Fig. 1. Sex and age distribution of the elderly men and women studied. Solid blocks, men; hatched blocks, women. All individuals were aged 84 years and older, except for 1 man aged 79.

Table 1

Apo E allele and genotype frequencies in the young population and in elderly men and women

Young Elderly men Elderly women No. (%) RR (95% CI) No. (%) RR (95% CI) Allele E2 40 (10%) 19 (10%) 0.95 (0.53–1.70) 27 (8%) 0.69 (0.41–1.15) E3 299 (75%) 150 (77%) 1.0 291 (82%) 1.0 E4 59 (15%) 27 (14%) 0.96 (0.58–1.58) 38 (11%) 0.66 (0.43–1.02) Genotype E2:3 35 (18%) 17 (17%) 0.92 (0.47–1.78) 19 (19%) 0.49 (0.24–1.00) E3:3 108 (54%) 57 (58%) 1.0 120 (68%) 1.0 E3:4 48 (24%) 19 (19%) 0.75 (0.40–1.40) 38 (18%) 0.71 (0.43–1.17)

The number of alleles or genotypes are indicated with proportions in parentheses. For genotype comparisons only E3:3, E3:4 and E3:2 were analysed, as the other genotypes were too rare to allow expected values of more than 5 in each cell of the (cid:120)2 contingency table. Genotypes in elderly women were different to the young population ((cid:120)2(cid:30)7.49, 2 d.f., PB0.05).

C-I allele and genotype frequencies at Hpa1 RFLP in the young population and in elderly men and elderly women

Young Elderly men Elderly women No. (%) RR (95% CI) No. (%) RR (95% CI) Allele 1 293 (75%) 150 (75%) 1.0 296 (82%) 1.0 2 97 (25%) 50 (25%) 1.01 (0.68–1.50) 66 (18%) 0.67 (0.47–0.95) Genotype 1:1 106 (54%) 57 (57%) 1.0 121 (67%) 1.0 1:2 81 (42%) 36 (36%) 0.83 (0.5–1.37) 54 (30%) 0.58 (0.38–0.89) 2:2 8 (4%) 7 (7%) 1.63 (0.56–4.73) 6 (3%) 0.66 (0.22–1.96)

The number of alleles or genotypes are indicated with proportions in parentheses. Allele 2, presence of cutting site. Allele and genotype frequencies were significantly different in elderly women compared to the young population ((cid:120)2(cid:30)4.49, 1 d.f., PB0.05; and (cid:120)2(cid:30)6.16, 2 d.f., PB0.05, respectively).

confirm associations at the apo E locus (Table 2). There were no significant differences in either allele or geno- type frequency distributions in the elderly men or the total elderly sample compared to the total young sam- ple. However, both allele and genotype frequencies were significantly different in the elderly women com- pared the young sample ((cid:120)2(cid:30)4.49, 1 d.f., P(cid:30)0.03; (cid:120)2(cid:30)6.16, 2 d.f., PB 0.05). The difference in genotype frequencies becomes non-significant if the frequencies in the young sample are constrained to be in Hardy-Wein- berg equilibrium and compared to the observed geno- type frequencies in the elderly women ((cid:120)2(cid:30)4.95, 2 d.f., P(cid:30)0.08).