Warensjö Eva, Ingelsson Erik, Lundmark Per, Lannfelt Lars, Syvänen Ann-Christine, Vessby Bengt, Risérus Ulf
Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala Science Park, 751 85 Uppsala, Sweden.
Obesity (Silver Spring). 2007 Jul;15(7):1732-40. doi: 10.1038/oby.2007.206.
Obesity and insulin resistance are major risk factors for metabolic diseases and are influenced by lifestyle and genetics. The lipogenic enzyme, stearoyl-coenzyme A-desaturase (SCD), is related to obesity. Further, SCD1-deficent mice are protected against obesity and insulin resistance. We hypothesized that genetic polymorphisms in the SCD1 gene would be associated with obesity, insulin sensitivity, and estimated SCD activity in humans.
The study population was 1143 elderly Swedish men taking part of a population-based cohort study, the Uppsala Longitudinal Study of Adult Men. Associations between single nucleotide polymorphisms and obesity (waist circumference and BMI), insulin sensitivity (assessed by hyperinsulinemic euglycemic clamp), and estimated SCD activity (fatty acid ratios) were analyzed using linear regression analysis.
Subjects homozygous for the rare alleles of rs10883463, rs7849, rs2167444, and rs508384 had decreased BMI and waist circumference and improved insulin sensitivity. The rare allele of rs7849 demonstrated the strongest effect on both insulin sensitivity [regression coefficient (beta)=1.19, p=0.007] and waist circumference (beta=-4.4, p=0.028), corresponding to 23% higher insulin sensitivity and 4 cm less waist circumference.
This study indicates that genetic variations in the SCD1 gene are associated with body fat distribution and insulin sensitivity, results that accord well with animal data. These results need confirmation in other populations with a larger sample size.
肥胖和胰岛素抵抗是代谢性疾病的主要危险因素，受生活方式和遗传因素影响。生脂酶硬脂酰辅酶A去饱和酶（SCD）与肥胖有关。此外，SCD1基因缺陷的小鼠可预防肥胖和胰岛素抵抗。我们推测，SCD1基因的遗传多态性与人类的肥胖、胰岛素敏感性及估计的SCD活性相关。
研究人群为1143名参与基于人群的队列研究——乌普萨拉成年男性纵向研究的瑞典老年男性。使用线性回归分析单核苷酸多态性与肥胖（腰围和体重指数）、胰岛素敏感性（通过高胰岛素正常血糖钳夹评估）及估计的SCD活性（脂肪酸比例）之间的关联。
rs10883463、rs7849、rs2167444和rs508384罕见等位基因的纯合子受试者体重指数和腰围降低，胰岛素敏感性改善。rs7849的罕见等位基因对胰岛素敏感性[回归系数（β）=1.19，p=0.007]和腰围（β=-4.4，p=0.028）的影响最强，相当于胰岛素敏感性提高23%，腰围减少4厘米。
本研究表明，SCD1基因的遗传变异与体脂分布和胰岛素敏感性相关，这一结果与动物数据相符。这些结果需要在其他更大样本量的人群中得到证实。
