TY - JOUR
T1 - Genome-wide association study identifies three common variants associated with serologic response to Vitamin E supplementation in men
AU - Major, Jacqueline M.
AU - Yu, Kai
AU - Chung, Charles C.
AU - Weinstein, Stephanie J.
AU - Yeager, Meredith
AU - Wheeler, William
AU - Snyder, Kirk
AU - Wright, Margaret E.
AU - Virtamo, Jarmo
AU - Chanock, Stephen
AU - Albanes, Demetrius
PY - 2012/5/1
Y1 - 2012/5/1
N2 - Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating a-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of a-tocopherol (50 mg/d) and had fasting serum a-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to a-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P=2.6×10-12) and rs2108622 on 19pter-p13.11 (P = 2.2 × 10-7), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 × 10-7). Combined, these SNP explain 3.4% of the residual variance in serum a-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., α-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology.
AB - Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating a-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of a-tocopherol (50 mg/d) and had fasting serum a-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to a-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P=2.6×10-12) and rs2108622 on 19pter-p13.11 (P = 2.2 × 10-7), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 × 10-7). Combined, these SNP explain 3.4% of the residual variance in serum a-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., α-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology.
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U2 - 10.3945/jn.111.156349
DO - 10.3945/jn.111.156349
M3 - Article
C2 - 22437554
AN - SCOPUS:84862108559
SN - 0022-3166
VL - 142
SP - 866
EP - 871
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 5
ER -