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单核苷酸多态性组合与健康男性胆钙化醇生物利用度的个体间差异相关。

A Combination of Single-Nucleotide Polymorphisms Is Associated with Interindividual Variability in Cholecalciferol Bioavailability in Healthy Men.

作者信息

Desmarchelier Charles, Borel Patrick, Goncalves Aurélie, Kopec Rachel, Nowicki Marion, Morange Sophie, Lesavre Nathalie, Portugal Henri, Reboul Emmanuelle

机构信息

NORT Nutrition Obesity and Thrombotic Risk, Aix-Marseille University, INRA National Institute for Agricultural Research, INSERM National Institute of Health and Medical Research, Marseille, France.

NORT Nutrition Obesity and Thrombotic Risk, Aix-Marseille University, INRA National Institute for Agricultural Research, INSERM National Institute of Health and Medical Research, Marseille, France;

出版信息

J Nutr. 2016 Dec;146(12):2421-2428. doi: 10.3945/jn.116.237115. Epub 2016 Oct 26.

DOI:10.3945/jn.116.237115
PMID:27798339
Abstract

BACKGROUND

Most people require dietary vitamin D to achieve the recommended concentration of 25-hydroxyvitamin D [25(OH)D] in the blood. However, the response to vitamin D supplementation is highly variable among individuals.

OBJECTIVE

We assessed whether the variability in cholecalciferol bioavailability was associated with single-nucleotide polymorphisms (SNPs) in candidate genes.

METHODS

In a single-group design, 39 healthy adult men with a mean ± SD age of 33 ± 2 y and mean ± SD body mass index (in kg/m) of 22.9 ± 0.3 were genotyped with the use of whole-genome microarrays. After an overnight fast, plasma 25(OH)D status was measured, and the subjects then consumed a meal that provided 5 mg cholecalciferol as a supplement. Plasma chylomicron cholecalciferol concentration was measured over 8 h, and cholecalciferol response was assessed by calculating the postprandial area under the curve. Partial least squares regression was used to test the association of SNPs in or near candidate genes (61 genes representing 3791 SNPs) with the postprandial cholecalciferol response.

RESULTS

The postprandial chylomicron cholecalciferol concentration peaked at 5.4 h. The cholecalciferol response was extremely variable among individuals (CV: 47%). It correlated with the chylomicron triglyceride (TG) response (r = 0.60; P < 0.001) but not with the fasting plasma 25(OH)D concentration (r = 0.04; P = 0.83). A significant (P = 1.32 × 10) partial least squares regression model that included 17 SNPs in 13 genes (including 5 that have been associated with chylomicron TG response) was associated with the variance in the cholecalciferol response.

CONCLUSION

In healthy men, there is a high interindividual variability in cholecalciferol bioavailability that is associated with a combination of SNPs located in or near genes involved in both vitamin D and lipid metabolism. This trial was registered at clinicaltrials.gov as NCT02100774.

摘要

背景

大多数人需要通过饮食摄入维生素D,以达到血液中25-羟基维生素D[25(OH)D]的推荐浓度。然而,个体对维生素D补充剂的反应差异很大。

目的

我们评估了胆钙化醇生物利用度的变异性是否与候选基因中的单核苷酸多态性(SNP)相关。

方法

在单组设计中,对39名健康成年男性进行基因分型,他们的平均年龄±标准差为33±2岁,平均体重指数(kg/m²)±标准差为22.9±0.3,采用全基因组微阵列进行基因分型。空腹过夜后,测量血浆25(OH)D水平,然后受试者食用一顿提供5mg胆钙化醇作为补充剂的餐食。在8小时内测量血浆乳糜微粒胆钙化醇浓度,并通过计算餐后曲线下面积评估胆钙化醇反应。采用偏最小二乘回归分析候选基因(61个基因,代表3791个SNP)内部或附近的SNP与餐后胆钙化醇反应之间的关联。

结果

餐后乳糜微粒胆钙化醇浓度在5.4小时达到峰值。个体间胆钙化醇反应差异极大(变异系数:47%)。它与乳糜微粒甘油三酯(TG)反应相关(r = 0.60;P < 0.001),但与空腹血浆25(OH)D浓度无关(r = 0.04;P = 0.83)。一个显著(P = 1.32×10)的偏最小二乘回归模型,该模型包含13个基因中的17个SNP(包括5个与乳糜微粒TG反应相关的SNP),与胆钙化醇反应的变异性相关。

结论

在健康男性中,胆钙化醇生物利用度存在高度个体差异,这与维生素D和脂质代谢相关基因内部或附近的SNP组合有关。该试验已在clinicaltrials.gov注册,注册号为NCT02100774。

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