Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.
Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.
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DOI：
10.1371/journal.pone.0052240
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
De Vivo I
中科院分区：
文献类型：
--
作者：
Du M;Prescott J;Cornelis MC;Hankinson SE;Giovannucci E;Kraft P;De Vivo I
尽管横断面研究已经将较高的身体质量指数（BMI）和2型糖尿病（T2D）与端粒缩短联系起来，但这些代谢条件是否在端粒生物学中起因果作用尚不清楚。因此，我们研究了高BMI或T2D的遗传易感是否与白细胞端粒长度（LTL）缩短有关。我们对来自护士健康研究的3,968名年龄在43-70岁之间的欧洲血统女性进行了分析，这些女性被选为全基因组关联研究和端粒与疾病研究的病例或对照。1989-1990年采集的外周血白细胞诊断前相对端粒长度采用定量PCR测定。我们结合多个风险变异的信息，根据BMI的32个位点附近的32个多态性和T2D的35个位点附近的36个多态性计算遗传风险评分。在调整年龄和病例对照状态后，BMI遗传风险评分与LTL之间没有相关性（β每标准差增加：- 0.01;SE: 0.02; P = 0.52）。同样，T2D遗传评分与LTL无关（β每标准差增加：−0.006;SE: 0.02; P = 0.69）。在这个欧洲血统的中老年妇女群体中，那些遗传上易患较高BMI或T2D的人并没有缩短端粒。虽然我们不能排除微弱或适度的影响，但我们的发现并不支持这些代谢条件和端粒动力学之间的强烈因果关系。
Although cross-sectional studies have linked higher body mass index (BMI) and type 2 diabetes (T2D) to shortened telomeres, whether these metabolic conditions play a causal role in telomere biology is unknown. We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL). We conducted an analysis of 3,968 women of European ancestry aged 43–70 years from the Nurses' Health Study, who were selected as cases or controls in genome-wide association studies and studies of telomeres and disease. Pre-diagnostic relative telomere length in peripheral blood leukocytes, collected in 1989–1990, was measured by quantitative PCR. We combined information from multiple risk variants by calculating genetic risk scores based on 32 polymorphisms near 32 loci for BMI, and 36 polymorphisms near 35 loci for T2D. After adjustment for age and case-control status, there was no association between the BMI genetic risk score and LTL (β per standard deviation increase: −0.01; SE: 0.02; P = 0.52). Similarly, the T2D genetic score was not associated with LTL (β per standard deviation increase: −0.006; SE: 0.02; P = 0.69). In this population of middle-aged and older women of European ancestry, those genetically predisposed to higher BMI or T2D did not possess shortened telomeres. Although we cannot exclude weak or modest effects, our findings do not support a causal relation of strong magnitude between these metabolic conditions and telomere dynamics.
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影响因子：
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作者：
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