Subjects

All subjects had been enrolled in the context of the AKEA study of Sardinian centenarians carried out between January 1 and December 31, 1997.11 One hundred and forty-one (141) centenarians underwent a full interview, and 129 donated a blood sample. The birth date of centenarians was checked by matching infor- mation from the census registry, baptism reg- istry of the local parish archive, social security documents, and the testimony of a first-degree relative. For each centenarian, a 60-year-old ~(41 ( 1 year) control of the same gender was ran- domly selected from the inhabitants of the same province. Overall, 290 sexagenarians randomly selected within the four Sardinian provinces were invited to join the study as con- trols and 154 agreed to participate and provide a blood sample. In addition, 24 ~~ 85-year-old sibs of centenarians were enrolled following the reported protocol. Written informed con- sent for enrolling in the study and personal data management was obtained from all the subjects according to Italian law.

TABLE 1. ANALYSIS OF HLA-DQA1* AND DQB1* ALLELE SHARING IN 24 CENTENARIAN-SIB PAIRS FROM SARDINIA

Nr of Centenarians Siblings alleles shared DQ DQ DQ DQ A1 B1 A1 B1 DQ DQ Sample Age Sex Typing Typing Sample Age Sex Typing Typing A1 B1 C1 104 F 01 01 05 06 S1 92 F 01 03 03 06 1 1 C2 105 F 01 05 02 05 S2 99 F 01 05 02 05 2 2 C3 103 M 01 01 05 06 S3 86 F 01 01 05 06 2 2 C4 101 M 01 02 02 05 S4 88 F 01 05 03 05 1 1 C5 106 M 01 02 03 03 S5 97 M 03 03 03 03 0 2 C6 104 M 01 05 02 03 S6 90 M 01 05 02 03 2 2 C7 107 M 01 01 05 05 S7a 85 F 01 01 05 05 2 2 S7b 88 F 01 05 05 03 1 1 C8 104 M 01 05 02 06 S8 91 M 03 04 03 04 0 0 C9 102 M 01 01 05 05 S9 81 M 02 03 02 03 0 0 C10 111 M 01 01 05 06 S10 96 F 01 01 03 03 2 0 C11 103 F 03 05 02 03 S11 91 F 01 05 02 05 1 1 C12 103 F 01 05 02 05 S12a 93 M 03 03 02 03 0 1 S12b 90 M 01 05 03 05 2 1 S12c 88 F 01 05 02 05 2 2 S12d 99 M 01 05 03 05 2 1 C13 103 F 01 05 02 06 S13 96 M 01 01 05 05 1 0 C14 101 F 01 05 03 05 S14a 94 F 01 05 03 05 2 2 S14b 92 F 01 01 03 05 1 2 C15 103 M 01 04 04 05 S15a 93 F 05 02 02 03 0 0 S15b 87 M 01 05 03 05 1 1 S15c 98 F 01 05 03 05 1 1 C16 103 F 03 05 03 03 S16 99 F 01 01 03 06 0 1 C17 103 M 01 02 03 03 S17 97 M 01 03 03 05 1 1

Statistical analysis (Pearson’s chi-squared test) demonstrated that observed and expected frequencies of allele iden- tity between centenarian and sibs were not significantly different for HLA-DQA1* and DQB1* alleles.

genes that contribute to human longevity is a powerful tool in mapping very strong effects of genes.10 Mapping of less effective but con- tributing genetic variation necessitates a larger sample.10 On the other hand, the sample size allowed the evaluation of DQA* or DQB1* al-  lele sharing among centenarians and 85-year- old sibs. Nine of twenty-four sibs shared two HLA-DQA1* and 8/24 shared two HLADQB1* alleles with centenarians, but statistical analy- sis demonstrates that the observed and ex- pected frequency of allele identity between centenarian and sibs was not significantly dif- ferent both for HLA-DQA1* and DQB1* loci, suggesting that genetic settlement at the HLA DQ region is indifferent regarding longevity. In conclusion, present and previous results5,16 seem to support the hypothesis that genes in- volved or associated with HLADQ-DR haplo- types have a marginal influence, if any, in de-

ACKNOWLEDGMENTS

The authors are grateful to Dr. Alessandra Errigo for help in patient recruitment and blood sample processing. The “Gruppo di Stu- dio sull’immunosenescenza” coordinated by Professor C. Caruso was funded by grants from MIUR, Rome (ex 40%, to C.C. and D.L.; ex 60% to G.C. and G.C.R.). The collaboration between this group and the Istituto Nazionale di Riposo e Cura per Anziani was enhanced by a coop- eration contract (longevity and elderly disabil- ity biological markers). Professor C. Franceschi was funded by MIUR, Rome (ex 40%), Ministry of Health projects (1998 and 2001 “Chronic dis- eases prevention in ageing: the model of cen- tenarians” and “Biological and genetic markers of successful and unsuccessful ageing”), and E.U. projects contract no. QLK6-CT-2001-0128 and N° QLK6-CT-2001-00310. Professor G. Baggio was funded by MIUR (ex 60%). Pro-

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