The Association between Methylenetetrahydrofolate Reductase (MTHFR) Mutations and Serum Biomarkers of Cardiac Health

Abstract

Background: Homocysteine (tHcy) has emerged as a new risk factor for cardiovascular diseases (CVD) The Methylenetetrahydrofolate reductase (MTHFR) polymorphisms are seen to give rise to high levels of tHcy which can be a causative factor in the progression of CVD due to its thrombogenic effect. Serum cardiac biomarkers help in the diagnosis, prognosis, or surveillance of CVD. The present study evaluated the association of the two MTHFR mutations, rs1801133 and rs1801131 with 16 well-established serum cardiac markers. Additionally, the influence of age and gender on the association of the two MTHFR polymorphisms with serum cardiac marker levels was also investigated. Methods: The study was carried out on 1295 individuals who visited Vibrant America Clinical Lab for regular or suspected CVD check-ups. The serological markers and genomic variant analysis were carried out as per the standard laboratory protocol under CLIA. The association between serological markers and the rs1801133 and rs1801131 genetic variants with respect to age and gender was evaluated using a one-way ANNOVA test. Results: No significant association was observed in tHcy levels with respect to gender, however, plasma total tHcy levels were higher in males than females. tHcy levels increased with increasing age in the wild and heterozygous genotypes for the mutations, rs1801133 and rs1801131. Additionally, the serum cardiac markers, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Cholesterol (CHOL), Apolipoprotein A (APOA), Apolipoprotein B (APOB), N-terminal (NT)-pro hormone BNP (BNPNT), LDL calculated (LDLCAL), Small Density Low Density Lipoprotein (SDLDL), APOBAR, Oxidised Low Density Lipoprotein (OXLDL), Lipoprotein (A) (LPA), Triglycerides (TRIG), and Lipoprotein-Associated Phospholipase (Lp-PLA2) Test (PLAC) showed significant associations with respect to gender and age for rs1801133 and rs1801131 (P < 0.05) However, these markers were seen to have different trends in correlation with gender and age. Conclusions: The present study reports the association of tHcy, HDL, LDL, CHOL, APOA, APOB, BNPNT, LDLCAL, SDLDL, APOBAR, OXLDL, LPA, TRIG, and PLAC with respect to age and gender for the mutations, rs1801133 and rs1801131. We observed that tHcy levels were high in males and the levels increased with increasing age in males for both polymorphisms. rs1801131 mutant males have high levels of triglyceride whereas rs1801133 mutant postmenopausal females showed high levels of cholesterol. Further analysis will be required to understand the pattern of association of the rest of the serum cardiac markers with age and gender for rs1801133 and rs1801131 mutations.