C47T polymorphism in manganese superoxide dismutase (MnSOD), antioxidant intake and survival.
OBJECTIVE
Manganese superoxide dismutase (MnSOD), an enzyme that catalyzes superoxide radical quenching, is hypothesized to protect against premature aging. A C47T transition in the MnSOD gene may affect the enzyme's distribution to the mitochondrion, a site of high oxidative stress. We examined the association between this polymorphism and survival.


METHODS
Individuals who donated a blood sample to the CLUE I and II campaigns in 1974 and 1989, respectively, and completed a food frequency questionnaire in 1989 (N=6151) were included in the analysis. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models. Mortality follow-up extended from 1989 to 2002.


RESULTS
MnSOD genotype distributions were 27% CC (wildtype homozygotes), 50% CT (heterozygotes) and 23% TT (variant homozygotes). TT and CT genotypes compared to the CC genotype were not associated with all-cause or cardiovascular disease mortality. A slight, but non-statistically significant higher risk of cancer mortality was observed for the CT (HR=1.13, 95% CI: 0.86-1.49) and TT (HR=1.24, 95% CI: 0.90-1.70) genotypes compared to CC genotype (p-trend=0.19).


CONCLUSIONS
We did not observe an association between the C47T polymorphism in the MnSOD gene and survival. These null associations were not modified by fruit and vegetable intake, cigarette smoking status, or body mass index.
Genkinger
Jeanine M
JM
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Building 2, Boston, MA, United States.
Platz
Elizabeth A
EA
Hoffman
Sandy C
SC
Strickland
Paul
P
Huang
Han-Yao
HY
Comstock
George W
GW
Helzlsouer
Kathy J
KJ
D000367:Age Factors; D000368:Aged; D000375:Aging; D000975:Antioxidants / Q000378:metabolism*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D002384:Catalysis; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012306:Risk; D012907:Smoking; D013482:Superoxide Dismutase / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome
D000975:Antioxidants; D013482:Superoxide Dismutase; D010100:Oxygen