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Int J Epidemiol.文章:男性睾酮和心血管病风险的遗传因素

某些研究显示男性低睾酮水平与某些心血管疾病的发生相关,但不同报道存在争议。本研究首先对289名香港青年进行睾酮相关的基因分型(rs10046, rs1008805和rs1256031)和睾酮水平检测,并构建遗传模型预测睾酮水平。进而采用孟德尔随机化和二重抽样(分离样本)的辅助变量方法对4212个广州生物样本库(Guangzhou Biobank Cohort Study)样本进行基因分型和睾酮水平预测。接下来采用多变量回归方法对预测的睾酮水平与心血管疾病风险因素进行关联分析。结果显示,预测的睾酮水平与收缩血压,舒张血压,空腹血糖,Framingham风险得分等4项因素都无关,但与较高的低密度脂蛋白-胆固醇(0.02 mmol/l, 95% CI 0.01 to 0.04)和较低的低密度脂蛋白-胆固醇水平(-0.01 mmol/l, 95% CI -0.02 to -0.001)存在显著关联。以上的计算都是在控制潜在的混淆因素(包括年龄、教育程度、吸烟情况、饮酒和体重指数)下进行的。总体上本研究发现不支持已报道的睾酮对男性心血管疾病或缺血性心脏病起保护作用的结果,而是认为较高的睾酮水平可能与对健康不利的脂肪状态有关。该研究已经发表在2013年International Journal of Epidemiology杂志上。本研究中Sequenom SNP分型检测工作由博奥生物集团有限公司完成。

补充:在最新的一项针对55,593例男性患者医疗保险资料的队列研究显示,与上一年相比,年龄≥65岁男性开始应用睾酮后90天内MI风险加倍,而对于有心脏疾病史的年轻男性,其风险增加近2倍[PLOS One. January 29, 2014; 9(1), e85805]。另外一项针对8,709例低睾酮水平男性患者的回顾性队列研究显示,与未接受睾酮治疗者相比,1,223例睾酮治疗者接受治疗1年内MI、卒中或死亡风险增加30%,治疗后2年相对风险是未治疗者的3倍,而3年则近6倍[JAMA. 2013 Nov 6;310(17):1829-36]。

原文摘要:
Genetically predicted testosterone and cardiovascular risk factors in men: a Mendelian randomization analysis in the Guangzhou Biobank Cohort Study.
BACKGROUND: Observationally lower testosterone is associated with an unhealthier cardiovascular (CVD) risk profile, but this association is open to confounding and reverse causality. The authors examined the association of testosterone with well-established cardiovascular disease (CVD) risk factors (blood pressure, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)cholesterol and fasting glucose) and the Framingham score using a Mendelian randomization analysis with a separate-sample instrumental variable estimator.
METHODS: To minimize reverse causality, a genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on three selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). Multivariable censored and linear regressions were used to examine the association of genetically predicted testosterone levels with CVD risk factors and Framingham score among 4212 older Chinese men from the Guangzhou Biobank Cohort Study.
RESULTS: Predicted testosterone was unrelated to systolic blood pressure [-0.11 mmHg, 95% confidence interval (CI) -0.70 to 0.48], diastolic blood pressure (0.04 mmHg, 95% CI -0.27 to 0.36), fasting glucose (0.02 mmol/l, 95% CI -0.02 to 0.06) or Framingham score (0.02, 95% CI -0.0001 to 0.03) but associated with higher LDL-cholesterol (0.02 mmol/l, 95% CI 0.01 to 0.04) and lower HDL-cholesterol (-0.01 mmol/l, 95% CI -0.02 to -0.001), after adjustment for potential confounders (age, education, smoking status, use of alcohol and body mass index).
CONCLUSIONS: Our findings did not corroborate observed protective effects of testosterone on cardiovascular risk factors or risk of ischaemic heart disease among men, but raises the possibility that higher testosterone may be associated with an unhealthier lipid profile. 
原文出处:
http://ije.oxfordjournals.org/content/early/2013/12/01/ije.dyt239.full