Relation between sex hormones and leucocyte telomere length in men with idiopathic pulmonary fibrosis.
Relation between sex hormones and leucocyte telomere length in men with idiopathic pulmonary fibrosis.
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男性特发性肺纤维化性激素与白细胞端粒长度的关系
DOI：
10.1111/resp.13871
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Fang C;Huang H;Zhang Q;Wang N;Jing X;Guo J;Ferianc M;Xu Z
IPF是一种以进行性肺瘢痕形成为特征的衰老相关肺部疾病。IPF患者常被鉴定为短端粒，但端粒酶编码突变只能解释少数病例。性激素在体外调节端粒酶活性，性激素水平与LTL相关。本研究的目的是探讨性激素是否与LTL相关，它们是否与端粒酶的遗传变异相互作用，以及雄激素代谢基因外显子的多态性是否与男性IPF患者的血浆睾酮浓度相关。在101例男性IPF受试者和51例年龄匹配的健康对照中进行了一项病例对照研究。对清晨血浆性激素进行定量，并使用全外显子组测序来鉴定端粒酶的罕见蛋白质改变变体和雄激素代谢基因外显子中的SNP。通过PCR分析LTL，并表示为T/S比。IPF组LTL、睾酮和DHT显著降低。在调整年龄和端粒酶相关基因的变异状态后，只有睾酮与LTL呈正相关（P = 0.001）。在端粒酶的罕见蛋白质改变变体和睾酮之间没有观察到显著的相互作用（P = 0.661）。雄激素代谢基因中无编码SNP与睾酮浓度显著相关。血浆睾酮与LTL相关，与年龄或罕见的端粒酶蛋白质改变变体无关。雄激素相关通路基因的遗传变异与雄激素浓度无关。需要进一步研究，以检查激素干预是否可能延缓男性IPF患者的端粒丢失。在这项病例对照研究中，我们探讨了性激素在IPF中的作用。我们发现，男性IPF患者血浆睾酮水平降低，血浆睾酮与LTL呈正相关。雄激素相关通路基因的编码变异与雄激素浓度无关。
IPF is an ageing‐related lung disorder featuring progressive lung scarring. IPF patients are frequently identified with short telomeres but coding mutations in telomerase can only explain a minority of cases. Sex hormones regulate telomerase activity in vitro and levels of sex hormones are related to LTL. The objective of this study was to explore whether sex hormones were associated with LTL, whether they interacted with genetic variants in telomerase and whether polymorphisms in the exon of androgen metabolism genes were associated with plasma testosterone concentrations in male IPF patients. A case–control study was performed on 101 male IPF subjects and 51 age‐matched healthy controls. Early morning plasma sex hormones were quantified, and whole‐exome sequencing was used to identify rare protein‐altering variants of telomerase and SNP in the exon of androgen metabolism genes. LTL was analysed by PCR and expressed as a T/S ratio. LTL, testosterone and DHT were decreased significantly in the IPF group. After adjustments for age and variant status in telomerase‐related genes, only testosterone was positively associated with LTL (P = 0.001). No significant interaction (P = 0.661) was observed between rare protein‐altering variants of telomerase and testosterone. No coding SNP in androgen metabolism genes were significantly associated with testosterone concentrations. Plasma testosterone is associated with LTL independent of age or rare protein‐altering variants of telomerase. No genetic variations of androgen‐related pathway genes are associated with androgen concentrations. Further studies are warranted to examine whether hormonal interventions might retard telomere loss in male IPF patients. In this case–control study, we explored the role of sex hormones in IPF. We found that plasma testosterone levels decreased in male patients with IPF, and plasma testosterone was positively associated with LTL. No coding variations of androgen‐related pathway genes were associated with androgen concentrations.
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