1 Average age and the number and ratio of subjects with hypertension, dialetes mellitus, or hyperlipidaemia

Table 1 Average age and the number and ratio of subjects with hypertension, dialetes mellitus, or hyperlipidaemia Genotype Total (Group I + group II) Group I Group II Sex Age categories No Mean age HT DM HL No Mean age HT DM HL No Mean age HT DM HL Male Younger (<60 y) 59 29.3 3 (5) 0 (0) 1 (2) 23 29.9 1 (4) 0 (0) 0 (0) 36 28.9 2 (6) 0 (0) 1 (3) Older (>60 to 74 y) 95 69.2 39 (41) 9 (9) 18 (19) 29 69.2 13 (45) 5 (17) 7 (24) 66 69.2 26 (39) 4 (6) 11 (17) Oldest (>75 y) 108 80.5 43 (40) 16 (15) 13 (12) 22 81.6 7 (32) 3 (14) 1 (5) 86 80.2 36 (42) 13 (15) 12 (14) Female Younger (<60 y) 45 33.4 0 (0) 0 (0) 0 (0) 19 38.5 0 (0) 0 (0) 0 (0) 26 29.7 0 (0) 0 (0) 0 (0) Older (>60 to 74 y) 106 69.8 40 (38) 12 (11) 37 (34) 42 71.2 17 (40) 7 (17) 14 (33) 64 68.9 23 (36) 5 (8) 23 (36) Oldest (>75 y) 99 80.2 31 (31) 8 (8) 30 (30) 30 79.7 8 (27) 2 (7) 10 (33) 69 80.4 23 (33) 6 (9) 20 (29)

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The ratio of subjects is expressed as (%) of subjects in each category. HT, hypertension; DM, diabetes mellitus; HL, hyperlipidaemia. Group I is the group of genotypes with a class L allele, which includes L/L, L/M, and L/S. Group II is the group of genotypes without a class L allele, which includes M/M, M/S, and

2 Genotype and allele frequencies at the polymorphic locus

Table 2 Genotype and allele frequencies at the polymorphic locus Allele frequencies Genotype frequencies Age categories L M•S Odds (95% Cl)† c 2, p value‡ Group I Group II Odds (95% Cl)† c 2, p value‡ Male c 2=9.76, p=0.008 c 2=6.91, p=0.032 Younger (<60 y) 27 (23%) 91 (77%) 1.98 (1.19 to 3.29)** 23 (39%) 36 (61%) 1.90 (1.04 to 3.49)+ Older (>60 to 74 y) 31 (16%) 159 (84%) 1.13 (0.70 to 1.85) 29 (31%) 66 (69%) 1.19 (0.68 to 2.07) Oldest (>75 y) 22 (10%) 194 (90%) 0.49 (0.29 to 0.82)** 22 (20%) 86 (80%) 0.50 (0.28 to 0.89)++ Female c 2=3.78, p=0.15 c 2=2.72, p=0.26 Younger (<60 y) 20 (22%) 70 (78%) 1.24 (0.71 to 2.15) 19 (42%) 26 (58%) 1.35 (0.70 to 2.20) Older (>60 to 74 y) 47 (22%) 165 (78%) 1.36 (0.87 to 2.11) 42 (40%) 64 (60%) 1.27 (0.76 to 2.14) Oldest (>75 y) 30 (15%) 168 (85%) 0.63 (0.39 to 1.00) 30 (30%) 69 (70%) 0.64 (0.38 to 1.10) Total c 2=11.8, p=0.0027 c 2=8.84, p=0.012 Younger (<60 y) 47 (23%) 161 (77%) 1.54 (1.06 to 2.24)* 42 (40%) 62 (60%) 1.57 (1.01 to 2.44)++ Older (>60 to 74 y) 78 (19%) 324 (81%) 1.27 (0.92 to 1.76) 71 (35%) 130 (65%) 1.26 (0.87 to 1.84) Oldest (>75 y) 52 (13%) 362 (87%) 0.56 (0.39 to 0.79)*** 52 (25%) 155 (75%) 0.57 (0.39 to 0.84)+++

Group I is the group of genotypes with a class L allele, which includes L/L, L/M, and L/S. Group II is the group of genotypes without a class L allele, which includes M/M, M/S, and S/S. †Odds for class L allele in the indicated age category versus those in all other age categories. ‡c 2 and p value were calculated for differences among the three age categories. §Odds for group I in the indicated age category versus those in all other age categories. *p<0.03, **p<0.01, ***p<0.001. +p<0.05, ++p<0.02, +++p<0.005.

in the HO-1 gene promoter may be a genetic factor that prevents the attainment of old age in Japanese males. There was no oldest male subject with the L/L genotype.On the other hand, the frequency of the L/S genotype in the oldest male subjects (8%) was significantly lower than that in younger (20%) and older (16%) male subjects. In contrast, in female subjects,the frequency of the L/S genotype in the oldest (12%) subjects did not differ significantly from that in the younger (16%) and older (16%) male subjects. These findings suggest that L/S genotypes may be an intermediate risk factor.

n grouped into three classes, according to the numbers of (GT)n repeats, as described previously8: class S alleles (<27 repeats), class M alleles (27-32 repeats), and class L alleles (33 < repeats). As shown in table 2, the proportion of allelic frequencies in class L was significantly lower in the total old- est subjects (52 (13%)) than in the total other younger (47 (23%)) and older (78 (19%)) subjects (df=2, c 2=11.8, p=0.0027) (table 2). Similarly, in the oldest male subjects, the proportion of allelic frequencies in class L was significantly lower than that in other male younger and older subjects (df=2, c 2=9.78, p=0.008). In the oldest female subjects, the proportion of allelic frequencies in class L was also lower than that in other female younger and older subjects, although there was no significant difference (df=2, c 2=0.38, p=0.15). The odds ratio for class L in the total oldest subjects versus the total younger and older subjects was 0.56 (95% CI 0.39 to 0.79, p<0.001). Particularly, the odds ratio for class L in the oldest males versus the younger males and older subjects was 0.49 (95% CI 0.29 to 0.82, p<0.01).

Because bilirubin has antioxidant activities,4 increased pro- duction of HO-1 may be associated with protection from the development of diseases induced by oxidative stress and may promote longevity in the male subjects with a small (GT) n repeat in the HO-1 gene promoter.



Authors’ affiliations

M Yamaya, K Nakayama, S Ebihara, H Hirai, H Sasaki, Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai 980-8574, Japan S Higuchi, National Institute on Alcoholism, Kurihama National Hospital,