Scola Letizia, Lio Domenico, Candore Giuseppina, Forte Giusi I, Crivello Antonio, Colonna-Romano Giuseppina, Pes Mario G, Carru Ciriaco, Ferrucci Luigi, Deiana Luca, Baggio Giovannella, Franceschi Claudio, Caruso Calogero
Gruppo di Studio dell'Immunosenescenza, Dipartimento di Biopatologia e Metodologie, Biomediche, Università di Palermo, Palermo, Italy.
Exp Gerontol. 2008 Feb;43(2):114-8. doi: 10.1016/j.exger.2007.06.007. Epub 2007 Jul 4.
Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a role in the association to diseases. Hence, we have evaluated, by amplification refractory mutation system/polymerase chain reaction (ARMS-PCR) the HLADQA1 and HLA-DQB1 allele frequencies in 123 centenarians and 92 controls from Sardinia to assess whether the association to HLA-DRB1 *15 allele may be due to the other genes involved in the HLA-DR,DQ haplotypes. The frequencies of HLA-DQA1, DQB1 haplotypes were not significantly modified in centenarians. Nevertheless by evaluating the frequency of DRB1 *15 linked haplotypes, we observed a not significant increase in centenarians of HLA-DQA1 *01, DQB1 *05 and HLA-DQA1 *01,DQB1 *06 haplotypes. These data suggest that these haplotypes might have a role in determining life span expectancy and longevity.
一些长寿的遗传决定因素可能存在于那些调节免疫反应的免疫系统基因的多态性中。许多长寿关联研究都将注意力集中在HLA（人类主要组织相容性复合体）多态性上，但结果并不一致。撒丁岛人是一个相对隔离的人群，是进行关联研究的合适群体。一些HLA-DR和DQ等位基因形成非常稳定的单倍型，连锁不平衡很强。在之前一项关于撒丁岛百岁老人的研究中，我们曾提出HLA-DRB1 *15等位基因可能与长寿存在微弱关联。HLA-DR、DQ单倍型连锁不平衡很强且保守性良好，在疾病关联中发挥作用。因此，我们通过扩增阻滞突变系统/聚合酶链反应（ARMS-PCR）评估了123名来自撒丁岛的百岁老人和92名对照中HLA-DQA1和HLA-DQB1等位基因频率，以评估与HLA-DRB1 *15等位基因的关联是否可能归因于参与HLA-DR、DQ单倍型的其他基因。百岁老人中HLA-DQA1、DQB1单倍型的频率没有显著改变。然而，通过评估与DRB1 *15连锁的单倍型频率，我们观察到百岁老人中HLA-DQA1 *01、DQB1 *05和HLA-DQA1 *01、DQB1 *06单倍型有不显著的增加。这些数据表明这些单倍型可能在决定预期寿命和长寿方面发挥作用。
