Association between Micronutrients and Hyperhomocysteinemia: A Case-Control Study in Northeast China

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular and cerebrovascular diseases where the plasma homocysteine (Hcy) concentration exceeds 15 µmol/L. HHcy is affected by vitamins B12, B6, and folic acid (fol); however, its relationship with other nutrients is not fully understood. We investigated the nutritional and genetic factors associated with HHcy and the possible dose-response relationships or threshold effects in patients in Northeast China. Genetic polymorphisms and micronutrients were tested with polymerase chain reaction and mass spectrometry, respectively. This trial was registered under trial number ChiCTR1900025136. The HHcy group had significantly more males and higher body mass index (BMI), methylenetetrahydrofolate reductase (MTHFR 677TT) polymorphism proportion, and uric acid, Zn, Fe, P, and vitamin A levels than the control group. After adjusting for age, sex, BMI, vitamin B12, fol, and MTHFR C677T, the lowest Zn quartile reduced the odds ratio of HHcy compared with the highest Zn quartile. The dose-response curves for the association between plasma Zn and HHcy were S-shaped. High plasma Zn concentrations were significantly correlated with high HHcy odds ratios, and the curve leveled off or slightly decreased. Most importantly, HHcy risk decreased with decreasing plasma Zn concentration; the threshold was 83.89 µmol/L. Conclusively, individuals residing in Northeast China, especially those with the MTHFR 677TT polymorphism, must pay attention to their plasma Zn and Hcy levels.