There was no significant correlation between

There was no significant correlation between the tHcy level and RBC folate level; therefore, we used two-way ANOVA to analyze the relative contributions of serum folate, the C677T genotype, and vitamin B12 to variations in tHcy concentrations. Intervention studies in humans taking folate and/or vitamin B12 supplements have shown that a plasma concentration of vitamin B12 greater than 300pM and a plasma folate concentration greater than 34nM could be the reference values for maintaining pppa stability. Therefore, these levels served as the thresholds for defining low vitamin levels. We accordingly found that the relative contribution of the three factors to tHcy level (in decreasing order) was folate, the C677T genotype, and vitamin B12 (Table 5). Moreover, there was a significant correlation between the tHcy concentration and low serum folate levels (r=−0.334, p=0.001) and low serum vitamin B12 levels (r=−0.212, p=0.046). However, there was no significant correlation between the tHcy concentration and high serum folate levels (r=0.051, p=0.763) and high vitamin B12 levels (r=−0.124, p=0.054).
Discussion Increased plasma tHcy levels are associated with several diseases such as cardiovascular disease, osteoporosis, dementia, Alzheimer\'s disease, pregnancy complications, and psychiatric disorders. Plasma tHcy is a sensitive marker of folate and vitamin B12 status, and defects in the metabolism of either factor may lead to increased plasma Hcy levels. Our study demonstrated a significant negative correlation between the mean serum levels of tHcy and the levels of folate and vitamin B12, thus supporting previous findings. Several human studies have shown that folate and vitamin B12 intake and biochemical status are important determinants of plasma tHcy concentrations. It has therefore been proposed that supplementation with vitamin B12 could help normalize blood tHcy levels. Thus, dietary folate deficiency and drugs that interfere with folate metabolism may lead to Hcy accumulation and the consequent cellular efflux of Hcy. In our study, the mean serum tHcy concentration was notably higher than previously reported concentrations. We speculate that this difference may have resulted from the unique cooking and dietary habits among people in Yunnan Province. People in Yunnan traditionally eat pickled and fried foods, which may not be conducive to the intake of folate and other vitamins. We confirmed that men had significantly higher serum tHcy concentrations than women, which is in line with the findings of previous reports. Nienaber-Rousseau et al believe that this finding may result from gene–sex interactions or may result from an inherent difference in creatinine levels, and that it may be influenced in men by increased alcohol consumption. Based on literature reports, the tHcy value in men is, on average, 1μM higher than in women. This difference could be caused by the larger muscle mass and thus greater creatine phosphate synthesis in men, a reduced effect of estrogens in women, and/or different Hcy metabolism processes between the sexes. By contrast, our results showed that the level of serum folate was significantly decreased in men than in women. A folate-B12 intervention trial revealed that the micronuclear frequency of peripheral blood lymphocytes was reduced by 37.1% in women and by 30% in men after supplementation, but the difference in men did not achieve statistical significance. It is possible that this differential response stems from an initial difference in vitamin status because vitamin intake is usually lower in men than in women; moreover, men consume more alcohol than women, which may further affect the absorption of the B vitamins. In addition, our results showed that individuals homozygous for the C677T variant allele (T) displayed elevated serum tHcy concentrations and that TT-homozygous individuals had the highest serum tHcy concentrations, whereas wild-type CC-homozygous individuals had the lowest serum tHcy concentrations. This result is consistent with the finding of Zidan et al, who found that the tHcy level was significantly increased in Egyptian children with coronary heart disease harboring the MTHFR 677TT and MTHFR 1298CC genotypes. Furthermore, de Bree et al and Ozarda et al found that healthy individuals with the TT genotype had a significantly higher tHcy concentration than those with the CC and CT genotypes. The increased tHcy concentrations could be attributed to thermolability induced in MTHFR, which results in dissociation of the active dimer into inactive monomers with a subsequent loss of flavin adenine dinucleotide-binding capacity. As a consequence, MTHFR would be unable to efficiently reduce 5,10-MTHF to 5-MTHF, which is necessary for the conversion of Hcy to methionine. Furthermore, the T allele frequency in our study was 35.2%. Schneider et al reported that the distribution of the MTHFR C677T mutation ranged 4.5%–44.9% in populations from Europe, Africa, the Middle East, Asia, Asia Minor, Australasia, and the Americas. The MTHFR C677T polymorphism is associated with increased tHcy levels and has been implicated in the increased risk of a wide range of adverse health conditions throughout life from birth defects to cardiovascular disease and osteoporosis in the elderly.