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 oldest subjects (52 (13%)) than in the total other younger (47 (23%)) and older (78 (19%)) subjects (df=2, c2=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, c2=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, c2=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 production 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.

The proportion of genotypic frequencies in group I with a class L allele (L/L, L/M, and L/S) was compared with that in group II without a class L allele (M/M, M/S, and S/S). The proportion of genotypic frequencies in group I was significantly lower in the oldest subjects (52 (25%)) than that in the total younger (42 (40%)) and