title: Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes.
abstract: 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.
authors: *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.
authors: Sara R
authors: SR
authors: Zwart
authors: *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.
authors: Jesse F
authors: JF
authors: Gregory
authors: *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.
authors: Steven H
authors: SH
authors: Zeisel
authors: *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.
authors: Charles R
authors: CR
authors: Gibson
authors: *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 scott.m.smith@nasa.gov.
authors: Thomas H
authors: TH
authors: Mader
authors: *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.
authors: Jason M
authors: JM
authors: Kinchen
authors: *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.
authors: Per M
authors: PM
authors: Ueland
authors: *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.
authors: Robert
authors: R
authors: Ploutz-Snyder
authors: *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.
authors: Martina A
authors: MA
authors: Heer
authors: *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 scott.m.smith@nasa.gov.
authors: Scott M
authors: SM
authors: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000728:Androgens / Q000235:genetics*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D013026:Space Flight; D014796:Visual Perception; D014815:Vitamins / Q000235:genetics*
chemical_list: D000728:Androgens; D014815:Vitamins; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D012696:Glycine Hydroxymethyltransferase; C520541:SHMT protein, human