Hegele R A
John P. Robarts Research Institute, University of Western Ontario, London, Canada.
Clin Biochem. 1998 Nov;31(8):609-12. doi: 10.1016/s0009-9120(98)00078-2.
Because there is interindividual variation in the metabolic response to diet, it important to find and evaluate candidate genes, which have common functional variants in the general population, and which may be determinants of interindividual differences in the response to components of the diet, such as dietary fat and fiber. One such candidate gene is FABP2, which encodes the intestinal fatty acid binding protein. This gene has a common variation in the coding sequence, which results in either alanine or threonine to be translated at residue 54. This amino acid variation has an in vitro functional impact. In addition, there have been several published associations with metabolic phenotypes, such as impaired glucose tolerance, obesity, altered plasma lipids and lipoproteins.
It is the FABP2 T54 variant that is almost always associated with the more deleterious phenotypic expression. Recent experiments have found that most of the inter-individual variation in the plasma lipoprotein response to dietary fiber could be attributed to the FABP2 A54T polymorphism. However, it is likely that differences in environment, such as the type of fatty acid or fiber consumed, might interact with functional differences in the gene product to produce phenotypic differences.
This means that more experimental work, using a variety of study samples and complementary approaches, is necessary before advocating routine testing of FABP2 genotype in people in order to determine their potential responsiveness to various dietary interventions, such as increased dietary soluble fiber.
由于个体对饮食的代谢反应存在差异,因此找到并评估候选基因非常重要。这些基因在普通人群中具有常见的功能变体,可能是个体对饮食成分(如膳食脂肪和纤维)反应差异的决定因素。脂肪酸结合蛋白2(FABP2)就是这样一个候选基因,它编码肠道脂肪酸结合蛋白。该基因在编码序列中有一个常见变异,导致在第54位残基处翻译出丙氨酸或苏氨酸。这种氨基酸变异具有体外功能影响。此外,已经有一些关于该基因与代谢表型(如糖耐量受损、肥胖、血浆脂质和脂蛋白改变)的关联报道。
几乎总是FABP2基因的T54变体与更有害的表型表达相关。最近的实验发现,血浆脂蛋白对膳食纤维反应的个体间差异大多可归因于FABP2基因A54T多态性。然而,环境差异(如所摄入脂肪酸或纤维的类型)可能与基因产物的功能差异相互作用,从而产生表型差异。
这意味着在提倡对人群进行FABP2基因分型的常规检测以确定其对各种饮食干预(如增加膳食可溶性纤维)的潜在反应性之前,需要使用各种研究样本和补充方法进行更多的实验工作。