PDF(Pubmed)
Abstract：
Introduction: Vitamin C is an essential nutrient. Sex differences in serum vitamin C concentrations have been observed but are not fully known. Investigation of levels of metabolites may help shed light on how dietary and other environmental exposures interact with molecular processes. O-methylascorbate and ascorbic acid 2-sulfate are two metabolites in the vitamin C metabolic pathway. Past research has found genetic factors that influence the levels of these two metabolites. Therefore, we investigated possible effect modification by sex of genetic variant-metabolite associations and characterized the biological function of these interactions. Methods: We included individuals of European descent from the Canadian Longitudinal Study on Aging with available genetic and metabolic data (n = 9004). We used linear mixed models to tests for genome-wide associations with O-methylascorbate and ascorbic acid 2-sulfate, with and without a sex interaction. We also investigated the biological function of the important genetic variant-sex interactions found for each metabolite. Results: Two genome-wide statistically significant (p value < 5 × 10-8) interaction effects and several suggestive (p value < 10-5) interaction effects were found. These suggestive interaction effects were mapped to several genes including HSD11B2, associated with sex hormones, and AGRP, associated with hunger drive. The genes mapped to O-methylascorbate were differently expressed in the testis tissues, and the genes mapped to ascorbic acid 2-sulfate were differently expressed in stomach tissues. Discussion: By understanding the genetic factors that impact metabolites associated with vitamin C, we can better understand its function in disease risk and the mechanisms behind sex differences in vitamin C concentrations.
摘要：
简介：维生素C是一种必需的营养素。已经观察到血清维生素C浓度的性别差异，但尚未完全了解。对代谢物水平的调查可能有助于阐明饮食和其他环境暴露如何与分子过程相互作用。O-甲基抗坏血酸盐和抗坏血酸2-硫酸盐是维生素C代谢途径中的两种代谢物。过去的研究发现影响这两种代谢物水平的遗传因素。因此,我们调查了遗传变异体-代谢物关联的性别可能的效应修饰，并表征了这些相互作用的生物学功能。方法：我们纳入了来自加拿大衰老纵向研究的欧洲血统个体，并提供了遗传和代谢数据（n=9004）。我们使用线性混合模型来测试与O-甲基抗坏血酸和抗坏血酸2-硫酸盐的全基因组关联，有和没有性别互动。我们还研究了每种代谢物的重要遗传变异-性别相互作用的生物学功能。结果：发现了两个具有统计学意义的全基因组（p值<5×10-8）相互作用效应和几个暗示性（p值<10-5）相互作用效应。这些暗示性相互作用效应被定位到几个基因，包括与性激素相关的HSD11B2，AGRP,与饥饿驱动有关。定位到O-甲基抗坏血酸盐的基因在睾丸组织中表达不同，定位到抗坏血酸2-硫酸盐的基因在胃组织中表达不同。讨论：通过了解影响与维生素C相关的代谢物的遗传因素，我们可以更好地了解其在疾病风险中的作用以及维生素C浓度性别差异背后的机制。
