脂肪酸谱和基因与2型糖尿病的相关性和队列研究

The prevalence of type 2 diabetes (T2DM) has increased significantly in recent decades, with an estimated 370 million adults having T2DM globally in 2030. Furthermore, an insidious epidemic of IFG/IGT also occurs. It is therefore crucial to identify modifiable risk factors that could contribute to the prevention of T2DM. The relationship between the polyunsaturated fatty acids (PUFAs), obtained from dietary survey and T2DM was controversial. The accuracy of the dietary survey was not as good as internal exposure (plasma marker). Few studies, which were mainly from western countries, have examined the associations of objectively measured circulating blood PUFAs with T2DM. Conclusions from these studies were not necessarily suitable for Chinese people owning to different dietary and genetic background. In addition, dose-response relationship between PUFAs and T2DM, and PUFAs- single nucleotide polymorphisms(SNPs) interaction with T2DM were also unknown so far. Based on case-control and nested case-control study, we investigated the association of PUFAs, genes, and PUFAs-genes interaction with T2DM. Gas chromatography was used to determine n-3 and n-6 PUFAs. MassARRAY was used to reveal SNPs, which were found from GWAS study and screened by snpinfo.niehs.nih.gov that affected the level of PUFAs. This study will provide an important group and individualized basis for dietary intake of different fatty acids in Chinese population.

近几十年以来，2型糖尿病的患病率快速上升，2030年全球将有3.7亿患者。此外，伴随IFG/IGT的隐匿性流行。因此寻找可调整的膳食方式来干预2型糖尿病非常重要。从膳食调查得到的不饱和脂肪酸与2型糖尿病的关系存在争议，膳食调查的准确性不如内暴露（血浆标志物）。研究血浆不饱和脂肪酸与2型糖尿病关系的研究很少，这些研究多来自西方。中国与欧洲人群的膳食及遗传背景有显著差异，这些结论对中国人群的指导有限。并且“剂量-效应”关系、与影响基因的交互作用仍不清楚。因此，研究者拟采用病例-对照和巢式病例-对照的研究方法探究不同种类脂肪酸的水平、基因、2型糖尿病的相关性。研究者采用气相色谱法测定n-3及n-6系列不饱和脂肪酸，MassARRAY检测从GWAS研究发现通过 snpinfo.niehs.nih.gov筛选的影响脂肪酸水平的基因。本研究将为中国人群膳食摄入不同的脂肪酸提供重要的群体和个体化的依据。

摘要.背景：多项独立研究表明，循环水平的奇链和超长链脂肪酸（VLSFAs）能有有益的影响，但结果是混合的。虽然饮食和代谢因素可能影响VLSFAs还不清楚，但此前的一项研究发现，VLSFAs浓度与丝氨酸棕榈酰转移酶长链碱基亚基3 （SPTLC3）基因变异之间存在相关性。.目的：研究血浆SFAs和SPTLC3基因rs680379多态性与代谢危险因素和2型糖尿病（T2D）的关系。.方法:采用气相色谱法测定898例T2D患者和1618例匹配对照组的血浆SFAs，采用MassArray系统对1178例T2D患者和1907例匹配对照组的SPTLC3基因rs680379多态性进行基因分型。用条件logistic回归估计ORs和95% CI。.结果：我们发现血浆奇链SFAs和VLSFAs与良好的血脂和胰岛素抵抗标志物谱相关。经多变量调整后，十五烷酸（15:0）与T2D的概率呈负相关（每一个SD的OR：0.63；95% CI：0.57，0.70），3个个体VLSFAs的测量值【花生酸（20：0），山茶酸（22：0）和木糖酸（24：0）】，ORs范围为0.60至0.72 （95% CIs范围为0.52至0.79）。在进一步调整甘油三酯后，3个个体的VLSFAs和T2D之间的关联减弱。与rs680379 GG基因型携带者相比，GA和AA基因型携带者T2D的OR值分别为0.81 （95% CI： 0.68, 0.97）和0.76 （95% CI： 0.61， 0.96）。.结论：血浆15:0和VLSFAs与T2D呈负相关。同时，与rs680379 GG基因型携带者相比，GA和AA基因型携带者的T2D发生率降低。有必要进行更多的调查来证实我们的发现。