Folate Deficiency and Gene Polymorphisms of MTHFR, MTR and MTRR Elevate the Hyperhomocysteinemia Risk

Area of Science:

• Genetics
• Cardiovascular Disease Epidemiology
• Nutritional Biochemistry

Background:

• Hyperhomocysteinemia (HHcy) is a recognized independent risk factor for cardiovascular diseases (CVDs).
• Investigating genetic predispositions and nutritional factors contributing to HHcy is crucial for understanding CVD risk.
• The interplay between homocysteine metabolism gene polymorphisms and folate status in hypertensive populations requires further elucidation.

Purpose of the Study:

• To examine the combined impact of specific homocysteine metabolism gene polymorphisms and folate deficiency on the risk of developing HHcy.
• To assess these effects within a cohort of Chinese hypertensive patients.

Main Methods:

• Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G using PCR-RFLP.
• Quantification of serum homocysteine (Hcy) via high-performance liquid chromatography.
• Measurement of serum folate levels using chemiluminescent immunoassay in 480 hypertensive patients.

Main Results:

• MTHFR C677T and MTR A2756G polymorphisms were independently associated with an elevated HHcy risk.
• The MTHFR A1298C polymorphism demonstrated a protective effect against HHcy.
• A synergistic effect was observed where the joint occurrence of risk genotypes, particularly all four, significantly amplified HHcy risk, an effect exacerbated by folate deficiency.

Conclusions:

• The study provides the first evidence that the combined effect of homocysteine metabolism gene polymorphisms and folate deficiency dramatically elevates HHcy risk.
• These findings highlight the critical role of genetic background and nutritional status in HHcy development among hypertensive individuals.
• Targeting both genetic predispositions and folate levels may be essential for mitigating HHcy and associated CVD risks.