男性循环睾酮、雌二醇、雌酮和性激素结合球蛋白浓度的遗传度：弗雷明汉心脏研究
The heritability of circulating testosterone, oestradiol, oestrone and sex hormone binding globulin concentrations in men: the Framingham Heart Study.
作者信息
Travison T G, Zhuang W V, Lunetta K L, Karasik D, Bhasin S, Kiel D P, Coviello A D, Murabito J M
机构信息
Research Program on Men's Health, Aging and Metabolism, Brigham and Women's Hospital, Boston, MA, USA.
出版信息
Clin Endocrinol (Oxf). 2014 Feb;80(2):277-82. doi: 10.1111/cen.12260. Epub 2013 Jun 27.
OBJECTIVE
Circulating testosterone, oestradiol and oestrone concentrations vary considerably between men. Although a substantial proportion of this variation may be attributed to morbidity and behavioural factors, these cannot account for its entirety, suggesting genetic inheritance as a potential additional determinant. The analysis described here was intended to estimate the heritability of male circulating total testosterone (TT), calculated free testosterone (cFT), oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG), along with the genetic correlation between these factors.
DESIGN
Cross-sectional, observational analysis of data from male members of the Offspring and Generation 3 cohorts of the Framingham Heart Study. Data were collected in the years 1998-2005.
PARTICIPANTS
A total of 3367 community-dwelling men contributed to the analysis, including 1066 father/son and 1284 brother pairs among other family relationships.
MEASUREMENTS
Levels of serum sex steroids (TT, E1 and E2) were measured by liquid chromatography-tandem mass spectrometry, SHBG by immunofluorometric assay and cFT by mass action equation. Heritability was obtained using variance components analysis with adjustment for covariates including age, diabetes mellitus, body mass index and smoking status.
RESULTS
Age-adjusted heritability estimates were 0·19, 0·40, 0·40, 0·30 and 0·41 for cFT, TT, E1, E2 and SHBG, respectively. Adjustment for covariates did not substantially attenuate these estimates; SHBG-adjusted TT results were similar to those obtained for cFT. Genetic correlation coefficients (ρG ) indicated substantial genetic association between TT and cFT (ρG = 0·68), between TT and SHBG (pG = 0·87), between E1 and E2 (ρG = 0·46) and between TT and E2 (ρG = 0·48).
CONCLUSION
Circulating testosterone, oestradiol and oestrone concentrations exhibit substantial heritability in adult men. Significant genetic association between testosterone and oestrogen levels suggests shared genetic pathways.
目的
男性体内循环睾酮、雌二醇和雌酮浓度存在显著差异。尽管这种差异的很大一部分可能归因于发病率和行为因素，但这些因素并不能完全解释其全部差异，这表明遗传因素可能是一个潜在的额外决定因素。此处描述的分析旨在估计男性循环总睾酮（TT）、计算游离睾酮（cFT）、雌酮（E1）、雌二醇（E2）和性激素结合球蛋白（SHBG）的遗传度，以及这些因素之间的遗传相关性。
设计
对弗雷明汉心脏研究后代队列和第三代队列男性成员的数据进行横断面观察分析。数据收集于1998年至2005年。
参与者
共有3367名社区居住男性参与分析，包括1066对父子和1284对兄弟，以及其他家庭关系。
测量
血清性类固醇（TT、E1和E2）水平通过液相色谱-串联质谱法测量，SHBG通过免疫荧光分析法测量，cFT通过质量作用方程计算。使用方差成分分析获得遗传度，并对年龄、糖尿病、体重指数和吸烟状况等协变量进行调整。
结果
cFT、TT、E1、E2和SHBG经年龄调整后的遗传度估计值分别为0.19、0.40、0.40、0.30和0.41。对协变量进行调整并没有显著减弱这些估计值；经SHBG调整后的TT结果与cFT的结果相似。遗传相关系数（ρG）表明TT与cFT之间（ρG = 0.68）、TT与SHBG之间（pG = 0.87）、E1与E2之间（ρG = 0.46）以及TT与E2之间（ρG = 0.48）存在显著的遗传关联。
结论
成年男性循环睾酮、雌二醇和雌酮浓度具有显著的遗传度。睾酮和雌激素水平之间的显著遗传关联表明存在共同的遗传途径。
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