Common genetic polymorphisms affect the human requirement for the nutrient choline
Common genetic polymorphisms affect the human requirement for the nutrient choline
复制标题
DOI：
10.1096/fj.06-5734com
复制
发表时间：
2006-07-01
期刊：
影响因子：
4.8
通讯作者：
Zeisel, Steven H.
中科院分区：
文献类型：
--
作者：
da Costa, Kerry-Ann;Kozyreva, Olga G.;Zeisel, Steven H.
人类饮食中缺乏必需的营养物质胆碱会导致器官功能障碍。我们假设参与胆碱代谢的基因中常见的单核苷酸多态性（snp）会影响这种营养物质的饮食需求。57人被喂食低胆碱饮食，直到他们出现器官功能障碍或长达42天。我们检测了与胆碱缺乏相关的器官功能障碍易感性相关的DNA snp等位基因。我们在磷脂酰乙醇胺n -甲基转移酶基因（ppt; -744 G -> C; rs12325817）的启动子区域发现了一个SNP，该SNP的23个C等位基因携带者中有18个（78%）在喂食低胆碱饮食时出现了器官功能障碍（优势比25，P = 0.002）。胆碱脱氢酶基因编码区的两个snp中的第一个（CHDH; +318 A -> C; rs9001）对胆碱缺乏症的易感性具有保护作用，而第二个CHDH变体（+432 G - >t; rs12676）与胆碱缺乏症的易感性增加有关。ppt编码区SNP （+5465 G -> A; rs7946）和甜菜碱：同型半胱氨酸甲基转移酶（BHMT） SNP （+742 G -> A; rs3733890）与胆碱缺乏症的易感性无关。确定影响胆碱饮食需求的常见多态性可以使我们确定需要确保足够的饮食胆碱摄入量的个体。
Humans eating diets deficient in the essential nutrient choline can develop organ dysfunction. We hypothesized that common single nucleotide polymorphisms (SNPs) in genes involved in choline metabolism influence the dietary requirement of this nutrient. Fifty-seven humans were fed a low choline diet until they developed organ dysfunction or for up to 42 days. We tested DNA SNPs for allelic association with susceptibility to developing organ dysfunction associated with choline deficiency. We identified an SNP in the promoter region of the phosphatidylethanolamine N-methyltransferase gene (PEMT; -744 G -> C; rs12325817) for which 18 of 23 carriers of the C allele (78%) developed organ dysfunction when fed a low choline diet (odds ratio 25, P = 0.002). The first of two SNPs in the coding region of the choline dehydrogenase gene (CHDH; +318 A -> C; rs9001) had a protective effect on susceptibility to choline deficiency, while a second CHDH variant (+432 G -> T; rs12676) was associated with increased susceptibility to choline deficiency. A SNP in the PEMT coding region (+5465 G -> A; rs7946) and a betaine: homocysteine methyltransferase (BHMT) SNP (+742 G -> A; rs3733890) were not associated with susceptibility to choline deficiency. Identification of common polymorphisms that affect dietary requirements for choline could enable us to identify individuals for whom we need to assure adequate dietary choline intake.