Zwart Sara R, Gregory Jesse F, Zeisel Steven H, Gibson Charles R, Mader Thomas H, Kinchen Jason M, Ueland Per M, Ploutz-Snyder Robert, Heer Martina A, Smith Scott M
*Division of Space Life Sciences, Universities Space Research Association, Houston, Texas, USA; Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida, USA; Nutrition Research Institute, University of North Carolina at Kannapolis, Kannapolis, North Carolina, USA; Coastal Eye Associates, Webster, Texas, USA; Cooper Landing, Alaska, USA; Metabolon, Incorporated, Durham, North Carolina, USA; Department of Clinical Science, University of Bergen, Bergen, Norway; **Department of Nutrition and Food Science, Nutritional Physiology, University of Bonn, Bonn, Germany; and Biomedical Research and Environmental Sciences Division, National Aeronautics and Space Administration Johnson Space Center, Houston, Texas, USA.
*Division of Space Life Sciences, Universities Space Research Association, Houston, Texas, USA; Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida, USA; Nutrition Research Institute, University of North Carolina at Kannapolis, Kannapolis, North Carolina, USA; Coastal Eye Associates, Webster, Texas, USA; Cooper Landing, Alaska, USA; Metabolon, Incorporated, Durham, North Carolina, USA; Department of Clinical Science, University of Bergen, Bergen, Norway; **Department of Nutrition and Food Science, Nutritional Physiology, University of Bonn, Bonn, Germany; and Biomedical Research and Environmental Sciences Division, National Aeronautics and Space Administration Johnson Space Center, Houston, Texas, USA
FASEB J. 2016 Jan;30(1):141-8. doi: 10.1096/fj.15-278457. Epub 2015 Aug 27.
Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine β-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that B-vitamin status and genetics were significant predictors of many of the ophthalmic outcomes that we observed. In one example, genetics trended toward improving (P = 0.10) and B-vitamin status significantly improved (P < 0.001) the predictive model for refractive change after flight. We document an association between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision changes. This line of research could lead to therapeutic options for both space travelers and terrestrial patients.
在执行国际空间站任务的部分宇航员中出现了眼部变化。视力下降被认为是太空飞行对人类健康的最大风险。受影响的宇航员在飞行前体内的一碳代谢物（如高半胱氨酸）浓度较高。我们推测，一碳代谢基因的遗传变异会导致宇航员易出现眼部变化。我们研究了甲硫氨酸合成酶还原酶（MTRR）、亚甲基四氢叶酸还原酶（MTHFR）、丝氨酸羟甲基转移酶（SHMT）和胱硫醚β合成酶（CBS）基因中的5种多态性及其与49名宇航员飞行后眼部变化的关联。MTRR 66位点的G等位基因数量和SHMT1 1420位点的C等位基因数量均与视觉障碍的几率有关。飞行前的脱氢表雄酮与棉絮斑呈正相关，飞行期间的血清睾酮反应与屈光变化有关。逐步回归分析表明，B族维生素状态和基因是我们观察到的许多眼部结果的重要预测因素。例如，基因对飞行后屈光变化预测模型有改善趋势（P = 0.10），而B族维生素状态则显著改善了该预测模型（P < 0.001）。我们记录了MTRR 66和SHMT1 1420多态性与太空飞行引起的视力变化之间的关联。这一系列研究可能会为太空旅行者和地球上的患者带来治疗选择。
