Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Eur J Hum Genet. 2011 Nov;19(11):1202-4. doi: 10.1038/ejhg.2011.104. Epub 2011 Jun 1.
Dietary essential polyunsaturated fatty acids (PUFAs) require fatty acid desaturases (FADS) for conversion to long-chain PUFAs (LCPUFAs), which are critical for many aspects of human health. A Δ6-desaturase deficiency in a single patient was attributed to an insertion mutation in the FADS2 promoter. Later population studies have shown this thymidine nucleotide (T) insertion to be a common polymorphism (rs3834458). We examined correlations between rs3834458 variants and fatty acid evidence of FADS2 activity in a cohort of rheumatoid arthritis patients selected for low or nil consumption of n-3 LCPUFA as fish or fish oil. The presence of the T allele was associated with higher FADS2 activity, as indicated by higher conversion of plasma n-3 PUFA to LCPUFA. However, the T-insertion/deletion polymorphism did not affect FADS2 promoter activity in luciferase reporter assays in HepG2 or NIH/3T3 cells. Our results indicate that the polymorphism rs3834458 does not appear to directly affect FADS2 promoter activity and is not responsible for a previously reported Δ6-desaturase deficiency.
膳食必需多不饱和脂肪酸（PUFAs）需要脂肪酸去饱和酶（FADS）转化为长链多不饱和脂肪酸（LCPUFAs），这对于人类健康的许多方面都至关重要。一名患者的Δ6-去饱和酶缺乏归因于 FADS2 启动子中的插入突变。后来的人群研究表明，这种胸苷核苷酸（T）插入是一种常见的多态性（rs3834458）。我们在一个选择低或不食用 n-3 LCPUFA（如鱼类或鱼油）的类风湿关节炎患者队列中，检查了 rs3834458 变异与 FADS2 活性的脂肪酸证据之间的相关性。T 等位基因的存在与 FADS2 活性更高相关，这表明血浆 n-3 PUFA 向 LCPUFA 的转化率更高。然而，在 HepG2 或 NIH/3T3 细胞中的荧光素酶报告基因检测中，T 插入/缺失多态性并不影响 FADS2 启动子活性。我们的结果表明，rs3834458 多态性似乎不会直接影响 FADS2 启动子活性，也不是先前报道的 Δ6-去饱和酶缺乏的原因。
