Red blood cell size is inversely associated with leukocyte telomere length in a large multi-ethnic population.
Red blood cell size is inversely associated with leukocyte telomere length in a large multi-ethnic population.
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DOI：
10.1371/journal.pone.0051046
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Garcia CK
中科院分区：
文献类型：
--
作者：
Kozlitina J;Garcia CK
尽管在患有各种血液疾病的患者中发现了编码端粒酶的蛋白质或RNA组分的基因突变，但对于来自普通人群的受试者，端粒长度对造血的影响还不太清楚。在这里，我们测量了从3157名受试者的循环白细胞中分离的基因组DNA的端粒长度，这些受试者的年龄从18岁到85岁不等，参加了一项基于多种族人群的大型研究，即达拉斯心脏研究2。较短的端粒长度与该队列中较低的红细胞计数略有相关，但与较大的平均红细胞大小显著相关（通过MCV测量），红细胞分布宽度（RDW）增加，血红蛋白水平升高和血小板计数降低，即使在校正年龄、性别和种族后也是如此（p值分别为<0.0001、<0.0001、0.0009和0.0016）。在多元回归模型中，我们发现端粒长度是MCV的显著协变量（p = 7.6×10−8），与年龄、种族、BMI、当前吸烟、饮酒、铁或同型半胱氨酸水平无关。 端粒长度对MCV变异的影响与吸烟或饮酒的影响相当，并且在老年人中更显着（>50岁的p=9.2×10−7 vs.<50岁的p=0.0006）。 据我们所知，这是第一份关于美国大城市人群中端粒长度和红细胞大小之间相关性的报告，并提示了衰老引起的大红细胞症的生物学机制。
Although mutations in the genes encoding either the protein or RNA component of telomerase have been found in patients with various blood disorders, the impact of telomere length on hematopoiesis is less well understood for subjects from the general population. Here we have measured telomere lengths of genomic DNA isolated from circulating leukocytes of 3157 subjects, ranging from 18 to 85 years of age, enrolled in a large multiethnic population based study, the Dallas Heart Study 2. Shorter telomere lengths are marginally associated with lower red blood cell counts in this cohort, but are significantly associated with larger mean red blood cell size (as measured by the MCV), increased red blood cell distribution width (RDW), higher hemoglobin levels and lower platelet counts, even after correction for age, gender and ethnicity (p-values of <0.0001, <0.0001, 0.0009 and 0.0016, respectively). In a multiple regression model we find that telomere length is a significant covariate of MCV (p = 7.6×10−8), independent of age, ethnicity, BMI, current smoking, alcohol consumption, iron or homocysteine levels. The effect of telomere length on MCV variation is comparable to the effect of smoking or alcohol consumption and is more significant in older individuals (p = 9.2×10−7 for >50 years vs. p = 0.0006 for <50 years of age). To our knowledge, this is the first report of an association between telomere length and red cell size in a large urban US population and suggests a biologic mechanism for macrocytosis of aging.
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DOI：
10.1164/rccm.200804-550oc
发表时间：
2008-10-01
影响因子：
24.7
作者：
Cronkhite, Jennifer T.;Xing, Chao;Garcia, Christine Kim
通讯作者：
Garcia, Christine Kim
DOI：
10.1056/nejmra0903373
发表时间：
2009-12-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Calado RT;Young NS
通讯作者：
Young NS
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
20.3
作者：
Beutler, E;West, C
通讯作者：
West, C
影响因子：
6.7
作者：
Den Elzen, Wendy P. J.;Martin-Ruiz, Carmen;Gussekloo, Jacobijn
通讯作者：
Gussekloo, Jacobijn