Skewed X inactivation and survival: a 13-year follow-up study of elderly twins and singletons
Skewed X inactivation and survival: a 13-year follow-up study of elderly twins and singletons
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DOI：
10.1038/ejhg.2011.215
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发表时间：
2012-03-01
影响因子：
5.2
通讯作者：
Christensen, Kaare
中科院分区：
文献类型：
--
作者：
Mengel-From, Jonas;Thinggaard, Mikael;Christensen, Kaare
在雌性哺乳动物中，两条X染色体中的一条在胚胎早期失活。因此，女性是两个细胞群体的嵌合体，一个是母亲的，另一个是父亲的X作为活跃的X染色体。偏斜的X失活是与50：50比率的显著偏离。在55-60岁以上的女性人群中，发现了偏度（DS）的增加。在这里，年龄相关的偏度和死亡率之间的关系进行了分析，在13年的随访研究中，500名妇女从三个队列（73-100岁的摄入量）。DS较低的女性的死亡率显著高于DS偏态的大多数女性（风险比：1.30; 95% CI：1.04-1.64）。X失活和死亡率之间的关联在双卵双胞胎中得到了复制，其中DS最低的同卵双胞胎在DS最高的双胞胎对内差异中也有统计学显著的先死亡趋势（比例：0.71; 95%CI：0.52-0.86）。这两个结果都表明，较低的DS与较高的死亡率相关。因此，我们建议，年龄相关的偏斜可能部分是由于人口的选择与死亡率较低的DS。欧洲人类遗传学杂志（2012）20，361-364; doi：10.1038/ejhg.2011.215; 2011年12月7日在线发表
In mammalian females, one of the two X chromosomes is inactivated in early embryonic life. Females are therefore mosaics for two cell populations, one with the maternal and one with the paternal X as the active X chromosome. A skewed X inactivation is a marked deviation from a 50:50 ratio. In populations of women past 55-60 years of age, an increased degree of skewing (DS) is found. Here the association between age-related skewing and mortality is analyzed in a 13-year follow-up study of 500 women from three cohorts (73-100 years of age at intake). Women with low DS had significantly higher mortality than the majority of women who had a more skewed DS (hazard ratio: 1.30; 95% CI: 1.04-1.64). The association between X inactivation and mortality was replicated in dizygotic twin pairs for which the co-twin with the lowest DS also had a statistically significant tendency to die first in the twin pairs with the highest intra-pair differences in DS (proportion: 0.71; 95% CI: 0.52-0.86). Both results suggest that lower DS is associated with higher mortality. We therefore propose that age-related skewing may be partly due to a population selection with lower mortality among those with higher DS. European Journal of Human Genetics (2012) 20, 361-364; doi:10.1038/ejhg.2011.215; published online 7 December 2011