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Genotyping

HLA-DR genotyping of the DNA for longevous groups was realized by reverse dot-blot with the Inno-Lipa DRB1 kit from Murex Diagnostics SA 68).

Statistical methods

The hypothesis that allelic distributions were heterogeneous among the different populations of controls was tested by a c 2 test. The same test was used to globally compare allelic distributions between the adult controls, VIE and SIB groups. Then the comparison of each allele frequency in VIE versus controls and SIB versus controls was performed by multivariate logistic regression. In addition to the variable coding for the presence or absence of the allele under study, the gender was included in the multivariate logistic regression model since it was a priori considered to be relevant, as well as the interaction between the two variables. The significance of the interaction was first tested by examining the changes in the deviation when interaction was added in the logistic model. When the interaction was significant, we analysed the effect of the studied allele and computed ORs separately for each gender. When the interaction did not reach significance, the analysis was done globally on both genders. Analyses were made either by a maximum likelihood algorithm or by exact Monte-Carlo methods when necessary (LogXact software, Cambridge). Since multiple comparisons were made, the Bonferroni corrections to maintain the overall type I error threshold at 0.05 would require that P-values be multiplied by the number of comparisons. Considering that 13 alleles were studied and that we compared controls versus centenarians and versus SIBs, a conservative stand would be to conclude that a difference is significant for P-values < 0.05/26 = 0.002. In the second study with a new cohort, however, we were justified in examining a priori the alleles DR7 and DR13, so no Bonferroni correction would be required.



We thank D. Alcalay, J. Delobel, M. Drouet, J. Seignalet and M. Tongio for providing genotypic data on their control populations. We thank C. Billon, L. Cazes, F. Dufour and M. Legrand for technical assistance with cell cultures and DNA extraction. We are grateful to J. Dausset and C. Finch for encouragement and comments. R.I. was supported by a grant from the ‘Fondation des Amis des Sciences’ and a ‘Poste Vert’ fellowship from INSERM.

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