HLA-DR alleles display sex-dependent effects on survival and discriminate between individual and familial longevity
HLA-DR alleles display sex-dependent effects on survival and discriminate between individual and familial longevity
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DOI：
10.1093/hmg/7.2.187
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发表时间：
1998-02-01
影响因子：
3.5
通讯作者：
Schächter, F
中科院分区：
文献类型：
--
作者：
Ivanova, R;Hénon, N;Schächter, F
为了重新评估HLA-DRB 1多态性对人类寿命个体间差异的贡献，我们比较了法国人群中长寿和成年对照组之间的基因型分布。长寿组包括两个独立的队列，共533名百岁老人和163名九十岁的兄弟姐妹。长寿组与对照组的等位基因分布有显著性差异，主要有3个等位基因：DR 7、DR 11和DR 13。多因素Logistic回归分析显示，长寿男性、百岁老人和90岁以上同胞的DR 7基因频率均高于对照组[OR=1.72（1.2-2.5）]，DR 11对寿命的影响与性别存在显著的交互作用，有长寿兄弟姐妹的女性患病率增高[OR = 2.03（1.4-3.0）]。DR 13基因在男性和女性百岁老人中的频率均增加[OR = 1.46（1.2-1.75）]。这些结果结合相关等位基因的其他病理生理效应进行了讨论。我们的数据支持三个HLA-DR等位基因在非常老的年龄生存的直接参与，两个等位基因特异性的影响寿命似乎取决于性别和家庭状况的聚集这一特点。后者是人类的原始发现。
In an effort to reassess the contribution of HLA-DRB1 polymorphisms to inter-individual variations of human longevity, we have compared their genotypic distributions between longevous and adult control groups in the French population. The longevous groups included two independent cohorts totalling 533 centenarians, and 163 nonagenarian siblings. Allelic distributions were significantly different between controls and longevous groups, Three individual alleles were mostly responsible for these differences: DR7, DR11 and DR13. Multivariate logistic analyses were performed in order to sort out interactions between gender-and age-specific genetic effects, DR7 frequency was elevated in longevous men, in centenarians as well as nonagenarian siblings [OR=1.72 (1.2-2.5)], DR11's influence on longevity displayed a significant interaction with sex, with an increase in women from longevous sibships [OR = 2.03 (1.4-3.0)]. DR13's frequency was increased in centenarians of both genders [OR = 1.46 (1.2-1.75)], These results are discussed in the context of other pathophysiological effects of the implicated alleles. Our data support the direct involvement of three HLA-DR alleles in survival at very old ages, Two allele-specific effects on longevity appear to depend on gender and one on familial status for aggregation of this trait. The latter is an original finding for humans.