Tromsø Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
Andrology. 2014 Mar;2(2):212-8. doi: 10.1111/j.2047-2927.2013.00174.x. Epub 2013 Dec 10.
Low testosterone levels are associated with metabolic and cardiovascular disease risk factor, and have been shown to predict type 2 diabetes mellitus (T2DM), myocardial infarction (MI) and all-cause mortality. It is not known if these associations are causal or not. Recently, it has been shown that the serum testosterone levels are associated with single-nucleotide polymorphisms (SNPs), and we therefore studied the associations between one of these SNPs, rs1799941 on the Sex Hormone-Binding Globulin (SHBG) gene, and MI, T2DM, cancer and death. DNA was prepared from men who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death and a randomly selected control group. For mortality, the observation time was set from 1994, and for the other endpoints from birth. The endpoint data were completed up to 2010-2013. Genetic analyses were successfully performed in 5309 men, of whom 1454 were registered with MI, 638 with T2DM, 1534 with cancer and in 2226 who had died. Men with the minor homozygote genotype had significantly higher levels of total testosterone (14.7%) and SHBG (24.7%) compared with men with the major homozygote genotype, whereas free testosterone levels did not differ significantly between the genotypes. The SNP rs1799941 was not significantly associated with MI, T2DM, cancer or mortality. Thus, our result does not support a causal relationship between total testosterone and SHBG and MI, T2DM, cancer or mortality, suggesting that low testosterone more likely is a marker of poor health.
睾丸激素水平与代谢和心血管疾病风险因素有关，并已被证明可预测 2 型糖尿病（T2DM）、心肌梗死（MI）和全因死亡率。目前尚不清楚这些关联是否具有因果关系。最近，已经表明血清睾丸激素水平与单核苷酸多态性（SNP）有关，因此我们研究了其中一种 SNP（位于性激素结合球蛋白（SHBG）基因上的 rs1799941）与 MI、T2DM、癌症和死亡之间的关联。从参加 1994-1995 年第四次特罗姆瑟研究调查的男性中提取 DNA，这些男性记录有 MI、T2DM、癌症或死亡终点事件以及随机选择的对照组。对于死亡率，观察时间从 1994 年开始，对于其他终点事件则从出生开始。终点数据截止到 2010-2013 年。对 5309 名男性进行了遗传分析，其中 1454 名男性患有 MI，638 名男性患有 T2DM，1534 名男性患有癌症，2226 名男性死亡。与主要纯合基因型男性相比，具有较小的纯合子基因型的男性总睾丸激素（14.7%）和 SHBG（24.7%）水平明显更高，而游离睾丸激素水平在基因型之间没有显著差异。SNP rs1799941 与 MI、T2DM、癌症或死亡率无显著相关性。因此，我们的结果不支持总睾丸激素和 SHBG 与 MI、T2DM、癌症或死亡率之间存在因果关系，这表明低睾丸激素更可能是健康状况不佳的标志物。
