Mao Jinyuan, Vanderlelie Jessica J, Perkins Anthony V, Redman Christopher W G, Ahmadi Kourosh R, Rayman Margaret P
Department of Endocrinology and Metabolism, the First Hospital of China Medical University, Shenyang, China; Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom;
School of Medical Science, Griffith Health Institute, Griffith University, Queensland, Australia; and.
Am J Clin Nutr. 2016 Jan;103(1):100-6. doi: 10.3945/ajcn.115.114231. Epub 2015 Dec 16.
Low selenium status in pregnancy has been associated with a number of adverse conditions. In nonpregnant populations, the selenium status or response to supplementation has been associated with polymorphisms in dimethylglycine dehydrogenase (DMGDH), selenoprotein P (SEPP1) and the glutathione peroxidases [cytosolic glutathione peroxidase (GPx1) and phospholipid glutathione peroxidase (GPx4)].
We hypothesized that, in pregnant women, these candidate polymorphisms would be associated with selenium status in early pregnancy, its longitudinal change, and the interindividual response to selenium supplementation at 60 μg/d.
With the use of stored samples and data from the United Kingdom Selenium in Pregnancy Intervention (SPRINT) study in 227 pregnant women, we carried out genetic-association studies, testing for associations between selenium status, its longitudinal change, and response to supplementation and common genetic variation in DMGDH (rs921943), SEPP1 (rs3877899 and rs7579), GPx1 (rs1050450) and GPx4 (rs713041). Selenium status was represented by the concentration of whole-blood selenium at 12 and 35 wk of gestation, the concentration of toenail selenium at 16 wk of gestation, and plasma glutathione peroxidase (GPx3) activity at 12 and 35 wk of gestation.
Our results showed that DMGDH rs921943 was significantly associated with the whole-blood selenium concentration at 12 wk of gestation (P = 0.032), which explained ≤2.0% of the variance. This association was replicated with the use of toenail selenium (P = 0.043). In unsupplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in whole-blood selenium from 12 to 35 wk of gestation (P = 0.005), which explained 8% of the variance. In supplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in GPx3 activity from 12 to 35 wk of gestation (P = 0.01), which explained 5.3% of the variance. Selenium status was not associated with GPx1, GPx4, or SEPP1 rs7579.
In agreement with previous studies, we show that the genetic variant rs921943 in DMGDH is significantly associated with selenium status in United Kingdom pregnant women. Notably, our study shows that women who carry the SEPP1 rs3877899 A allele are better able to maintain selenium status during pregnancy, and their GPx3 activity increases more with supplementation, which suggests better protection from low selenium status. The SPRINT study was registered at www.isrctn.com as ISRCTN37927591.
孕期低硒状态与多种不良情况相关。在非孕期人群中，硒状态或对补充剂的反应与二甲基甘氨酸脱氢酶（DMGDH）、硒蛋白P（SEPP1）以及谷胱甘肽过氧化物酶[胞质谷胱甘肽过氧化物酶（GPx1）和磷脂谷胱甘肽过氧化物酶（GPx4）]的基因多态性有关。
我们假设，在孕妇中，这些候选基因多态性与孕早期的硒状态、其纵向变化以及对每天60μg硒补充剂的个体间反应有关。
利用来自英国孕期硒干预（SPRINT）研究中227名孕妇的储存样本和数据，我们开展了基因关联研究，检测硒状态、其纵向变化以及对补充剂的反应与DMGDH（rs921943）、SEPP1（rs3877899和rs7579）、GPx1（rs1050450）和GPx4（rs713041）中常见基因变异之间的关联。硒状态通过妊娠12周和35周时全血硒浓度、妊娠16周时趾甲硒浓度以及妊娠12周和35周时血浆谷胱甘肽过氧化物酶（GPx3）活性来表示。
我们的结果显示，DMGDH rs921943与妊娠12周时的全血硒浓度显著相关（P = 0.032），该基因变异对变异的解释率≤2.0%。使用趾甲硒重复验证了这种关联（P = 0.043）。在未补充硒的女性中，SEPP1 rs3877899与妊娠12周至35周期间全血硒的百分比变化显著相关（P = 0.005），该基因变异对变异的解释率为8%。在补充硒的女性中，SEPP1 rs3877899与妊娠12周至35周期间GPx3活性的百分比变化显著相关（P = 0.01），该基因变异对变异的解释率为5.3%。硒状态与GPx1、GPx4或SEPP1 rs7579无关。
与先前的研究一致，我们表明DMGDH中的基因变异rs921943与英国孕妇的硒状态显著相关。值得注意的是，我们的研究表明，携带SEPP1 rs3877899 A等位基因的女性在孕期更能维持硒状态，并且她们的GPx3活性在补充硒后增加得更多，这表明她们对低硒状态有更好的保护作用。SPRINT研究已在www.isrctn.com上注册，注册号为ISRCTN37927591。
