Analysis of HLA-DQA, HLA-DQB frequencies in a group of Sardinian centenarians
A. Crivello, D. Lio, G. Candore, G.I. Forte, L. Scola, G. Colonna-Romano, M.G. Pes, C. Carru, L. Ferrucci, L. Deiana, G. Baggio, C. Franceschi, C. Caruso
Gruppo di Studio dell'Immunosenescenza, Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Corso Tukory 211, 90134 Palermo
Some studies suggest that genetic determinants of longevity might
reside in the polymorphisms for genes that regulate immune responses as
HLA genes. Some HLA alleles or haplotypes that confer resistance to
infectious disease respectively via peptide presentation or via antigen
non specific stimulation, have been selected all through evolution.
Some of the highly conserved haplotypes are composed by the HLA-DRDQ
alleles and in some instances HLA-DQ alleles play a central role in the
association to disease. The relatively homogeneous Sardinian
population, an ancient genetic isolate having a gene pool characterized
by a relative little genetic flow from the various populations invading
the island during the last 3000 years, may represent a suitable sample
for association studies addressed to dissect the complex traits as
longevity. So we have evaluated the HLA-DQA1 and HLA-DQB1 allele
frequencies in 123 centenarians from Sardinia and 92 controls
randomly selected from the inhabitants of the same country. HLA-DQ
alleles typing was carried out by PCR-SSP. HLA-DQA1 and HLA-DQB1
allele frequencies were evaluated by gene count and haplotype
frequencies calculated by a maximum likelihood algorithm (Arlequin
Software, University of Geneva). 2 x 2 tables were constructed to
determine statistical significance (2 test with Yate's
correction) of differences in HLA haplotype frequencies between
centenarians and controls. Obtained P values were multiplied for the
number of alleles under study (Bonferroni's correction). Distribution
frequency analysis suggested that within each group, the haplotype
distributions were consistent with those predicted by the
Hardy-Weinberg equilibrium. The frequencies of HLA- DQA1-DQB1 were not
significantly different in centenarians (both in women and in men)
respect to controls. Moreover, we have investigated the association
between heterozygous HLA genotypes and longevity, considering that
heterozygote subjects are thought more fit for survival than homozygote
ones. On the basis of haplotype distribution, we have been able to show
an equal percentage of heterozygote subjects in centenarians and
controls (11.4 vs. 15.2). Therefore these data suggest that II class
HLA DQ genes allele could not influencing life span expectation
according to the other reports. On the other hand with the exception of
IDDM and Celiac Disease most of studies on association among HLA class
II loci and disease have individuated the HLA-DR and not -DQ loci as
the major susceptibility component for ageing associated diseases.
Key words:
HLA, LONGEVITY, SARDINIA, CENTENARIANS
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