Objectives
Recently, elevated homocysteine was reported to be associated with frailty in cross-sectional studies. However, whether homocysteine is causally associated with frailty is unknown. Here, we explore the inter-relationships between five non-synonymous genetic variants of homocysteine metabolic four genes, plasma homocysteine levels, and frailty.
Results
The percentage of high homocysteine (>15μmol/L) is 33.3%. Two functional variants that decrease methylenetetrahydrofolate reductase (MTHFR) activities, C677T (Ala222Val, rs1801133) and A1298C (Glu429Ala, rs1801131), were significantly associated with increased homocysteine levels (β=−1.16, p=0.01; and β=1.46, p<0.001, respectively). In addition, homocysteine increase gradually from CC-CC, CC-AC, CT-AC, CT-AA, CC-AA, to TT-AA genotypes of the C677T-A1298C combinations. The five polymorphisms in the homocysteine metabolic gene was not associated with frailty. However, homocysteine was significantly associated with frailty with an OR of 2.27 (95% 1.36–3.78) for high homocysteine after adjusting for multiple confounding factors.