Neither direct comparisons between genotypes (Table 1, Table 3, Table 4) nor three-way analyses revealed significant differences between case/control genotypic pools at REN, PARP, SOD2 loci. Therefore HUMREN4, PARP (gt) and SOD2(c/t) poly- 845nt 401nt morphisms are not markers of longevity. On the other hand positive results were found at the THO locus. The loss of LL genotypes in male centenarians with respect to controls in both southern and northern Italy is evident (Table 2), although statistical significance is borderline in northern Italian males when adjustment for multiple comparison is made. In any case, we agree with Rothman28 that reducing the type 1 error for null

Table 4 SOD2 locus. Genotypic numbers and relative frequencies of the SOD2 (C/T) polymorphism

North Italy Males Controls Centenarians Genotypes (n=46) (n=25) P No. Rel. freq St. err No. Rel. freq St. err CC 12 0.261 0.065 7 0.280 0.090 1 CT 23 0.500 0.074 10 0.400 0.098 0.464 TT 11 0.239 0.063 8 0.320 0.093 0.576 Females Controls Centenarians Genotypes (n=60) (n=80) P No. Rel. freq St. err No. Rel. freq St. err CC 11 0.183 0.050 12 0.150 0.040 0.649 CT 30 0.500 0.064 41 0.512 0.056 1 TT 19 0.317 0.060 27 0.337 0.053 0.857 South Italy Males Controls Centenarians Genotypes (n=40) (n=19) P No. Rel. freq St. err No. Rel. freq St. err CC 6 0.150 0.056 1 0.053 0.051 0.411 CT 19 0.475 0.079 12 0.631 0.111 0.282 TT 15 0.375 0.076 6 0.316 0.107 0.775 Females Controls Centenarians Genotypes (n=40) (n=43) P No. Rel. freq St. err No. Rel. freq St. err CC 6 0.150 0.056 7 0.163 0.056 1 CT 21 0.525 0.079 24 0.558 0.076 0.827 TT 13 0.325 0.074 12 0.279 0.068 0.811

P: probability of falsely rejecting the hypothesis of equal genotype frequency (CC or CT or TT) in centenarians and a =0.017.

by INRCA (Ancona, Italy) and by the National Research Council, Target Project on Aging (94,00408, PF40).

associations increases the type II error for those associations that are not null. On the other hand, it is well known that the number of males who survive to very old age is much lower than that of females. If a certain genotype is unfavourable to longevity only (or primarily) in males, a gender gap in longevity should ensue. Our results suggest that the THO locus could be one of those which correlate with gender effect in

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