Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbruecke, Nuthetal, Germany.
PLoS One. 2012;7(11):e48338. doi: 10.1371/journal.pone.0048338. Epub 2012 Nov 6.
Stearoyl-CoA desaturase-1 (SCD1) is an enzyme involved in lipid metabolism. In mice and humans its activity has been associated with traits of the metabolic syndrome, but also with the prevention of saturated fatty acids accumulation and subsequent inflammation, whereas for liver fat content inconsistent results have been reported. Thus, variants of the gene encoding SCD1 (SCD1) could potentially modify metabolic risk factors, but few human studies have addressed this question.
In a sample of 2157 middle-aged men and women randomly drawn from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1 tagging-single nucleotide polymorphisms (rs1502593, rs522951, rs11190480, rs3071, rs3793767, rs10883463 and rs508384) and 5 inferred haplotypes with frequency >5% describing 90.9% of the genotype combinations in our population, on triglycerides, body mass index (BMI), waist circumference (WC), glycated haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT) and fetuin-A.
No significant associations between any of the SNPs or haplotypes and BMI, WC, fetuin-A and hs-CRP were observed. Associations of rs10883463 with triglycerides, GGT and HbA1c as well as of rs11190480 with ALT activity, were weak and became non-significant after multiple-testing correction. Also associations of the haplotype harbouring the minor allele of rs1502593 with HbA1c levels, the haplotype harbouring the minor alleles of rs11190480 and rs508384 with activity of ALT, and the haplotype harbouring the minor alleles of rs522951, rs10883463 and rs508384 with triglyceride and HbA1C levels and GGT activities did not withstand multiple-testing correction.
These findings suggest that there are no associations between common variants of SCD1 or its inferred haplotypes and the investigated metabolic risk factors. However, given the results from animal models, heterogeneity of human SCD1 warrants further investigation, in particular with regard to rare variants.
硬脂酰辅酶 A 去饱和酶 1（SCD1）是一种参与脂质代谢的酶。在小鼠和人类中，其活性与代谢综合征的特征有关，但也与防止饱和脂肪酸积累和随后的炎症有关，而对于肝脂肪含量则有不一致的结果报告。因此，SCD1 基因（SCD1）的变体可能潜在地改变代谢危险因素，但很少有人类研究解决这个问题。
在欧洲前瞻性癌症与营养调查的波茨坦队列中，我们从 2157 名中年男女中随机抽取了一个样本，研究了 7 个 SCD1 标记单核苷酸多态性（rs1502593、rs522951、rs11190480、rs3071、rs3793767、rs10883463 和 rs508384）和 5 个推断的单倍型（频率>5%，描述我们人群中 90.9%的基因型组合）对甘油三酯、体重指数（BMI）、腰围（WC）、糖化血红蛋白（HbA1c）、高敏 C 反应蛋白（hs-CRP）、γ-谷氨酰转移酶（GGT）、丙氨酸氨基转移酶（ALT）和胎球蛋白-A 的影响。
未发现任何 SNP 或单倍型与 BMI、WC、胎球蛋白-A 和 hs-CRP 之间存在显著关联。rs10883463 与甘油三酯、GGT 和 HbA1c 以及 rs11190480 与 ALT 活性的关联较弱，并且在多重检验校正后变得不显著。此外，携带 rs1502593 次要等位基因的单倍型与 HbA1c 水平、携带 rs11190480 和 rs508384 次要等位基因的单倍型与 ALT 活性、以及携带 rs522951、rs10883463 和 rs508384 次要等位基因的单倍型与甘油三酯和 HbA1C 水平和 GGT 活性之间的关联也没有通过多重检验校正。
这些发现表明，SCD1 的常见变体或其推断的单倍型与研究的代谢危险因素之间没有关联。然而，鉴于动物模型的结果，人类 SCD1 的异质性需要进一步研究，特别是稀有变异。
