女性循环中的睾酮和性激素结合球蛋白浓度是可遗传的：弗雷明汉心脏研究。
Circulating testosterone and SHBG concentrations are heritable in women: the Framingham Heart Study.
机构信息
Sections of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston University School of Public Health, Boston, Massachusetts 02118, USA.
出版信息
J Clin Endocrinol Metab. 2011 Sep;96(9):E1491-5. doi: 10.1210/jc.2011-0050. Epub 2011 Jul 13.
CONTEXT
Many factors influence the concentration of circulating testosterone and its primary binding protein, SHBG. However, little is known about the genetic contribution to their circulating concentrations in women, and their heritability in women is not well established.
OBJECTIVE
Our objective was to estimate the heritability of circulating total testosterone (TT), free testosterone (FT), and SHBG in women in families from the Framingham Heart Study.
METHODS
Women in the Framingham Heart Study who were not pregnant, had not undergone bilateral oophorectomy, and were not using exogenous hormones were eligible for this investigation. TT was measured using liquid chromatography tandem mass spectrometry and SHBG using an immunofluorometric assay (Delfia-Wallac), and FT was calculated. Heritability estimates were calculated using variance-components methods in Sequential Oligogenic Linkage Analysis Routines (SOLAR) and were adjusted for age, age(2), body mass index (BMI), BMI(2), diabetes, smoking, and menopausal status. Bivariate analyses were done to assess genetic correlation between TT, FT, and SHBG.
RESULTS
A total of 2685 women were studied including 868 sister pairs and 688 mother-daughter pairs. Multivariable adjusted heritability estimates were 0.26 ± 0.05 for FT, 0.26 ± 0.05 for TT, and 0.56 ± 0.05 for SHBG (P < 1.0 × 10(-7) for all). TT was genetically correlated with SHBG [genetic correlation coefficient (ρG) = 0.31 ± 0.10] and FT (ρG = 0.54 ± 0.09), whereas SHBG was inversely correlated with FT (ρG = -0.60 ± 0.08).
CONCLUSION
Circulating TT, FT, and SHBG concentrations in women are significantly heritable, underscoring the importance of further work to identify the specific genes that contribute significantly to variation in sex steroid concentrations in women. The strong shared genetic component among pairs of TT, FT, and SHBG concentrations suggests potential pleiotropic effects for some of the underlying genes.
背景
许多因素会影响循环睾酮及其主要结合蛋白 SHBG 的浓度。然而，人们对女性循环浓度的遗传贡献知之甚少，其遗传性也尚未得到很好的确立。
目的
本研究旨在评估弗雷明汉心脏研究（Framingham Heart Study）中女性家族成员的循环总睾酮（TT）、游离睾酮（FT）和 SHBG 的遗传度。
方法
本研究纳入了未怀孕、未行双侧卵巢切除术且未使用外源性激素的弗雷明汉心脏研究中的女性。TT 采用液相色谱串联质谱法（liquid chromatography tandem mass spectrometry）检测，SHBG 采用免疫荧光测定法（Delfia-Wallac）检测，FT 则通过计算得出。采用 SOLAR（Sequential Oligogenic Linkage Analysis Routines）中的方差成分方法计算遗传度估计值，并根据年龄、年龄的平方、体重指数（BMI）、BMI 的平方、糖尿病、吸烟和绝经状态进行调整。通过双变量分析评估 TT、FT 和 SHBG 之间的遗传相关性。
结果
共纳入 2685 名女性，包括 868 对姐妹和 688 对母女。多变量调整后的遗传度估计值分别为 FT 为 0.26 ± 0.05，TT 为 0.26 ± 0.05，SHBG 为 0.56 ± 0.05（所有 P 值均<1.0×10(-7)）。TT 与 SHBG 呈正相关（遗传相关系数 ρG 为 0.31 ± 0.10），与 FT 呈正相关（ρG 为 0.54 ± 0.09），而 SHBG 与 FT 呈负相关（ρG 为 -0.60 ± 0.08）。
结论
女性循环 TT、FT 和 SHBG 浓度具有显著的遗传性，这突显了进一步研究确定对女性性激素浓度具有显著影响的特定基因的重要性。TT、FT 和 SHBG 浓度之间存在较强的共同遗传成分，提示其中一些潜在的基因存在多效性。
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