Methylenetetrahydrofolate reductase 677C>T and methionine synthase 2756A>G mutations: no impact on survival, cognitive functioning, or cognitive decline in nonagenarians.
BACKGROUND
Several reports have shown an association between homocysteine, cognitive functioning, and survival among the oldest-old. Two common polymorphisms in the genes coding for methylenetetrahydrofolate reductase (MTHFR 677C>T) and methionine synthase (MTR 2756A>G) have an impact on plasma homocysteine level.


METHODS
We examined the effect of the MTHFR 677C>T and MTR 2756A>G genotypes on baseline cognitive functioning, cognitive decline over 5 years measured in three assessments, and survival in a population-based cohort of 1581 nonagenarians. Cognitive functioning was assessed by using the Mini-Mental State Examination (MMSE) and five brief cognitive tests (cognitive composite).


RESULTS
There are no differences in MMSE score (p =.83) or in cognitive composite (p =.56) at intake as a function of genotype tested by analysis of variance, whereas sex and social group have a impact on MMSE (p < or =.03), and social group on the cognitive composite (p <.01). The mean MMSE was lower for women than for men. However, considering the group participating in all three assessments, there were no sex-related differences in MMSE (p =.34). The cognitive decline in the group participating in all three assessments was investigated using regression models for the relationship between cognitive performance and genotype, age, sex, and social group and revealed no significant difference. Furthermore, the MTHFR 677T and MTR 2756A heterozygous and homozygous genotype had no significant impact on survival, with hazard ratios of 1.05 (95% confidence interval [CI], 0.93-1.17), 0.93 (95% CI, 0.77-1.14), 1.05 (95% CI, 0.94-1.18), and 0.97 (95% CI, 0.74-1.28).


CONCLUSIONS
MTHFR and MTR genotypes are not associated with cognitive functioning, cognitive decline, or survival among nonagenarians.
Bathum
Lise
L
Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, DK-5000 Odense C, Denmark. lisebathum@dadlnet.dk
von Bornemann Hjelmborg
Jacob
J
Christiansen
Lene
L
McGue
Matt
M
Jeune
Bernard
B
Christensen
Kaare
K
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000225:Adenine; D000369:Aged, 80 and over; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D003596:Cytosine; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D015577:Geriatric Assessment; D006147:Guanine; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D015996:Survival Rate; D013941:Thymine
D005819:Genetic Markers; D006147:Guanine; D003596:Cytosine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D000225:Adenine; D013941:Thymine