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首页> 外文期刊>Cytokine >Age- and gender-specific epistasis between ADA and TNF-alpha influences human life-expectancy.
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Age- and gender-specific epistasis between ADA and TNF-alpha influences human life-expectancy.

机译：ADA和TNF-α之间的年龄和性别特异性上位性会影响人类的预期寿命。

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Aging is a complex phenotype with multiple determinants but a strong genetic component significantly impacts on survival to extreme ages. The dysregulation of immune responses occurring with increasing age is believed to contribute to human morbidity and mortality. Conversely, some genetic determinants of successful aging might reside in those polymorphisms for the immune system genes regulating immune responses. Here we examined the main effects of single loci and multi-locus interactions to test the hypothesis that the adenosine deaminase (ADA) and tumor necrosis factor alpha (TNF-alpha) genes may influence human life-expectancy. ADA (22G>A, rs73598374) and TNF-alpha (-308G>A, rs1800629; -238G>A, rs361525) functional SNPs have been determined for 1071 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes: for men (women), the first class consists of individuals<66 years old (<73 years old), the second class of individuals 66-88 years old (73-91 years old), and the third class of individuals>88 years old (>91 years old). Single-locus analysis showed that only ADA 22G>A is significantly associated with human life-expectancy in males (comparison 1 (age class 2 vs. age class 1), O.R. 1.943, P=0.036; comparison 2 (age class 3 vs. age class 2), O.R. 0.320, P=0.0056). Age- and gender-specific patterns of epistasis between ADA and TNF-alpha were found using Generalized Multifactor Dimensionality Reduction (GMDR). In comparison 1, a significant two-loci interaction occurs in females between ADA 22G>A and TNF-alpha -238G>A (Sign Test P=0.011). In comparison 2, both two-loci and three-loci interaction are significant associated with increased life-expectancy over 88 years in males. In conclusion, we report that a combination of functional SNPs within ADA and TNF-alpha genes can influence life-expectancy in a gender-specific manner and that males and females follow different pathways to attain longevity.
机译：衰老是具有多个决定因素的复杂表型，但是强大的遗传成分会显着影响到极端年龄的存活率。人们认为，随着年龄的增长而发生的免疫反应失调会导致人类发病和死亡。相反，成功衰老的一些遗传决定因素可能存在于调节免疫应答的免疫系统基因的那些多态性中。在这里，我们检查了单基因座和多基因座相互作用的主要作用，以检验腺苷脱氨酶（ADA）和肿瘤坏死因子α（TNF-α）基因可能影响人类预期寿命的假设。已针对来自意大利中部（18-106岁）的1071名不相关健康个体确定了ADA（22G> A，rs73598374）和TNF-alpha（-308G> A，rs1800629; -238G> A，rs361525）的功能性SNP，分为三部分根据人口统计信息定义的特定性别年龄段，并考虑到性别之间的不同存活：对于男性（女性），第一类包括<66岁的个体（<73岁），第二类是66-88的个体年龄（73-91岁），以及第三类个人> 88岁（> 91岁）。单基因座分析表明，只有ADA 22G> A与男性的预期寿命显着相关（比较1（年龄2与年龄1），或1.943，P = 0.036;比较2（年龄3与年龄2）。年龄2），或0.320，P = 0.0056）。使用广义多因素降维（GMDR）发现了ADA和TNF-α之间的年龄和性别特异性上位性模式。在比较1中，雌性在ADA 22G> A与TNF-α-238G> A之间发生显着的两位相互作用（符号测试P = 0.011）。在比较2中，男性在两个场所和三个场所的交互作用均与88岁以上的预期寿命增加显着相关。总之，我们报告说，ADA和TNF-α基因中功能性SNP的组合可以以性别特定的方式影响预期寿命，并且男性和女性遵循不同的途径来达到长寿。

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