Basic Science and Pathogenesis

Area of Science:

• Genetics
• Biochemistry
• Gerontology

Background:

• Methylenetetrahydrofolate reductase (MTHFR) is crucial for folate metabolism and homocysteine regulation.
• MTHFR gene variants are linked to elevated homocysteine, a risk factor for cognitive decline.
• The TATA Longitudinal Study of Aging (TLSA) cohort was used to investigate MTHFR gene variations.

Purpose of the Study:

• To investigate genetic variations in the MTHFR gene and its flanking regions.
• To determine the association between MTHFR variants and homocysteine levels in an elderly Indian population.
• To explore potential genetic predispositions to altered homocysteine metabolism in aging.

Main Methods:

• Genotype-phenotype analysis was performed on 376 participants from the TLSA cohort after quality control.
• PLINK v1.9.0 was used for analysis, accounting for age, gender, vitamin B12, and folic acid levels.
• Statistical methods included Mann-Whitney and Chi-Squared tests for demographic and homocysteine level comparisons.

Main Results:

• The TLSA cohort (N=696, mean age 73.6 years) exhibited elevated mean homocysteine levels (19.4 μmol/L).
• An intronic MTHFR variant (1:11793135) with an allele frequency of 0.0213 showed a significant association with higher homocysteine levels (p=0.01867).
• The analysis adjusted for age, gender, vitamin B12, and folic acid levels.

Conclusions:

• A significant association was found between MTHFR variant 1:11793135 and elevated homocysteine levels in an elderly Indian population.
• These findings suggest a potential genetic predisposition to altered homocysteine metabolism in aging individuals.
• The study highlights the importance of genetic screening for MTHFR polymorphisms and targeted interventions to mitigate cognitive decline.