Table 1. Apolipoprotein E (ApoE) Genotypes in Relation to Sex and Age in 1344 Healthy Elderly Persons and 64 Centenarians

Men (N ¼ 592) Women (N ¼ 752) All (N ¼ 1344) Age Range Group (N) (Mean 6 SD) e2/ p OR (95% CI) e4/ e2/ p OR (95% CI) e4/ e2/ p OR (95%CI) e4/ All 22–90 11.49% — — 19.76% 11.44% — — 20.35% 11.45% — — 20.08% (n ¼ 1344) (41.31 6 13.63) (n ¼ 68) (n ¼ 117) (n ¼ 86) (n ¼ 153) (n ¼ 154) (n ¼ 270) Group 1 Age   30 16.35% .270 1.519 20.19% 12.23% ..999 1.338 22.34% 13.70% ..999 1.537 21.58% (n ¼ 292) (27.29 6 2.10) (n ¼ 17) (0.732–3.151) (n ¼ 21) (n ¼ 23) (0.615–2.911) (n ¼ 42) (n ¼ 40) (0.913–2.585) (n ¼ 63) Group 2 30 , age , 45 7.72% ,.001 3.550 18.79% 10.88% .253 1.528 18.43% 9.38% ,.001 2.356 18.60% (n ¼ 629) (36.76 6 3.94) (n ¼ 23) (1.824–6.907) (n ¼ 56) (n ¼ 36) (0.736–3.173) (n ¼ 61) (n ¼ 59) (1.457–3.811) (n ¼ 117) Group 3 45 -SIA age , 60 8.41% .005 3.233 24.30% 9.82% .197 1.713 23.93% 9.26% .002 2.390 24.07% (n ¼ 270) (50.44 6 4.17) (n ¼ 9) (1.377–7.589) (n ¼ 26) (n ¼ 16) (0.751–3.909) (n ¼ 39) (n ¼ 25) (1.347–4.240) (n ¼ 65) Groups 1 þ 2 þ 3 Age , 60 9.63% ,.001 2.787 20.24 11.00% .238 1.509 20.82% 10.41 .001 2.099 20.57% (n ¼ 1191) (37.54 6 8.78) (n ¼ 49) (1.544–5.031) (n ¼ 103) (n ¼ 75) (0.759–2.999) (n ¼ 142) (n ¼ 124) (1.351–3.260) (n ¼ 245) Group 4 60 —LIA age  90 22.89% Reference 16.87% 15.71% Reference 15.71% 19.61% Reference 16.34% (n ¼ 153) (70.71 6 7.51) (n ¼ 19) (n ¼ 14) (n ¼ 11) (n ¼ 11) (n ¼ 30) (n ¼ 25) Centenarians 98   age   108 27.78% .659 1.296 0.00% 30.43% .059 2.347 1.6% 29.69% .105 1.731 1.56% (n ¼ 64) (100.28 6 1.86) (n ¼ 5) (0.410–4.098) (n ¼ 0) (n ¼ 14) 0.955–5.768 (n ¼ 1) (n ¼ 19) (0.887–3.378) (n ¼ 1)

Note: SD ¼ standard deviation; OR ¼ odds ratio; CI ¼ confidence interval.

7.51 years). This distribution reflected that of the healthy population living in the Apulia region as reported by the ISTAT (Istituto Italiano di Statistica) Report 2002 (25).

tenarians (p ¼ .792). However, after dividing the partici- pants according to sex, a significant difference in e2 frequency was found in men 60–90 years of age compared to men less than 60 years of age, that is, Group 4 versus Groups 1–3 (22.89% vs 9.63, p , .001), Group 4 versus Group 3 (22.89% vs 8.41%, p ¼ .005), and Group 4 versus Group 2 (22.89% vs 7.72%, p , .001). Moreover, the e2 frequency found in men of Group 4 was quite similar to that found in centenarian males (22.89% vs 27.78%, p ¼ .659). No differences were observed in e2 frequency in women (data not shown). No significant differences in e4 frequency were found across the age groups in the overall study sample or in separate groups of men and women (data not shown). Notably, only one participant (a woman) in the centenarian group had an e4 allele. Logistic regression analysis (Table 2) confirmed this outcome, showing a significant role of sex in the association of e2 and old age, that is, participants in Group 4 (crude odds ratio [OR] ¼ 1.897; 95% CI, 1.227–2.931; sex-adjusted OR ¼ 1.015; 95% CI, 0.530–1.944) and centenarians (crude OR ¼ 3.263; 95% CI, 1.860–5.722; sex-adjusted OR ¼ 4.096; 95% CI, 2.178–7.703).

ApoE genotype frequencies in the total sample of 1344 participants did not differ significantly from the expected Hardy–Weinberg frequencies (p ¼ .364): The estimated allele frequencies were e2 ¼ 0.060 (95% CI, 0.051–0.070), e3¼0.836 (95% CI, 0.821–0.850), and e4¼0.104 (95% CI, 0.093–0.116). Similarly, apoE genotype frequency in cente- narians did not differ significantly from the expected Hardy– Weinberg frequencies (p ¼ .422): The estimated allele frequencies were e2 ¼ 0.148, e3 ¼ 0.844, and e4 ¼ 0.008.

groups (Table 1), a significantly higher e2 frequency was found in Group 4, that is, participants aged from 60 to 90 years, compared to participants younger than 60 years, that is, participants of Group 1 þ Group 2 þ Group 3 (19.61% vs 10.41%, p ¼ .001). This finding was mainly due to a higher prevalence of e2 in Group 4 than in Group 3 (19.61% vs 9.26%, p ¼ .002) and Group 2 (19.61% vs 9.38%, p , .001). No significant difference in e2 frequency was found between Group 4 and centenarians (19.61% vs 29.69%, p ¼ .105). No participants showing genotypes e2/e2, e2/e4, or e4/e4 were observed in the centenarian group. In a linear model, no association was found between apoE genotypes and age.

The ACE genotype frequencies of the total 1344- participant group did not significantly differ from the expected Hardy–Weinberg frequencies (p ¼ .299): Esti- mated allele frequencies were I ¼ 0.349 (95% CI, 0.331– 0.367) and D ¼ 0.651 (95% CI, 0.633–0.669). Similarly, ACE genotype frequencies in centenarians did not differ

In a sex 3 genotype analysis, no significant differences were found in the 1344 participants (p ¼ .983) or in cen-

Table 2. Association of Apolipoprotein E (ApoE) Alleles With Age in 1344 Healthy Elderly Persons and 64 Centenarians

e2 e4 Crude Values Adjusted Values Crude Values Adjusted Values Group (N) p OR (95% CI) p OR (95% CI) p OR (95% CI) p OR (95% CI) Group 1 (n ¼ 292) .410 1.173 (0.803–1.715) .563 1.154 (0.711–1.873) .258 1.201 (0.875–1.649) .035 1.506 Group 2 (n ¼ 629) .003 0.604 (0.433–0.843) .072 0.678 (0.444–1.035) .581 0.927 (0.710–1.212) .181 0.792 Group 3 (n ¼ 270) .094 0.683 (0.437–1.067) .404 0.791 (0.455–1.373) .026 1.434 (1.045–1.970) .041 1.502 Group 4 (n ¼ 153) .004 1.897 (1.227–2.931) .964 1.015 (0.530–1.944) .335 0.801 (0.510–1.257) .119 0.602 Centenarians (n ¼ 64) ,.001 3.263 (1.860–5.722) ,.001 4.096 (2.178–7.703) .006 0.063 (0.009–0.457) .039 0.124

Note: OR ¼ odds ratio; CI ¼ confidence interval.

Table 3. Angiotensin-Converting Enzyme (ACE) Genotypes in Relation to Sex and Age in 1344 Healthy Elderly Persons and 64 Centenarians