A common methylenetetrahydrofolate reductase gene mutation and longevity

Area of Science:

• Genetics
• Cardiovascular Disease Epidemiology
• Population Genetics

Background:

• The methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation is present in about 12% of Caucasians.
• Individuals with the TT genotype (homozygotes) exhibit mild hyperhomocysteinemia, a known risk factor for cardiovascular disease.
• If the MTHFR C677T mutation significantly contributes to premature death, its frequency would be lower in elderly populations compared to younger ones.

Purpose of the Study:

• To investigate the association between the MTHFR C677T mutation and premature death.
• To compare the prevalence of the MTHFR C677T mutation in newborn and elderly Swedish populations.
• To conduct a meta-analysis of existing studies to determine the mutation's impact on longevity.

Main Methods:

• Genotyping for the MTHFR C677T mutation was performed on 220 Swedish newborns and 222 elderly individuals (aged 80-108 years).
• Allele and genotype frequencies were calculated for both age groups.
• A meta-analysis combined data from this study with three previous studies, totaling 1388 elderly and 1415 younger subjects.

Main Results:

• The allele frequency of the MTHFR C677T mutation was 29.1% in newborns and 27.0% in the elderly.
• The mutant homozygote (TT) frequency was 10.0% in newborns and 9.5% in the elderly.
• The meta-analysis showed an odds ratio of 0.87 (95% CI, 0.69-1.11) for the TT genotype to reach old age compared to the CC genotype, and 0.83 (95% CI, 0.66-1.04) compared to both CC and CT genotypes.

Conclusions:

• The MTHFR C677T mutation's prevalence is similar in newborns and the elderly.
• The study does not provide evidence that the MTHFR C677T mutation is a strong risk factor for diseases causing premature death.
• The findings suggest the MTHFR C677T mutation does not significantly impact lifespan in the studied populations.