Genetic variants determining body fat distribution and sex hormone-binding globulin among Chinese female young adults 遗传因素决定了中国青少年女性体脂分布和血清性激素结合球蛋白水平

Background Measures of body fat distribution (i.e. waist : hip ratio [WHR]) are major risk factors for diabetes, independent of overall adiposity. The genetic variants related to body fat distribution show sexual dimorphism and particularly affect females. Substantial literature supports a role for sex hormone-binding globulin (SHBG) in the maintenance of glucose homeostasis. The aim of the present study was to examine the association of the genetic risk score of body fat distribution with SHBG levels and insulin resistance in young (14–30 years) Chinese females. Methods In all, 675 young Chinese females were evaluated in the present study. A genetic risk score (GRS) was calculated on the basis of 12 established variants associated with body fat distribution. The main outcome variable was serum SHBG levels and homeostasis model assessment of insulin resistance (HOMA-IR). Results The GRS of body fat distribution was significantly associated with decreasing serum SHBG levels (P = 0.018), independent of body mass index and WHR. In addition, the GRS and SHBG showed additive effects on HOMA-IR (P = 0.004). Conclusions The GRS of body fat distribution reflects serum SHBG levels, and the GRS and SHBG jointly influence the risk of insulin resistance. 摘要 背景：体脂分布的测量（以WHR为衡量指标）独立于全身性肥胖，是糖尿病的主要危险因素。与体脂分布相关的遗传变异作用存在性别差异，其对女性的影响尤为明显。大量文献证实了性激素结合球蛋白（sex hormone-binding globulin，SHBG）在维持葡萄糖稳态方面具有一定的作用。本研究旨在中国青少年女性中（14–30岁）探讨体脂分布的遗传风险评分与SHBG和胰岛素抵抗的关系。 方法：本研究共纳入675名中国青年女性。根据与体脂分布显著相关的12个变异位点计算其遗传风险评分（genetic risk score，GRS），主要结果变量为血清SHBG水平和胰岛素抵抗指数（homeostasis model assessment of insulin resistance，HOMA-IR）。 结果：体脂分布的GRS与血清SHBG水平降低显著相关（P = 0.018），独立于BMI和WHR。此外，GRS和SHBG对HOMA-IR有协同作用（P = 0.004）。 结论：体脂分布的遗传风险评分可反映血清SHBG的水平，上述两者共同影响胰岛素抵抗的风险。