Background Serum homocysteine (sHcy) is currently well recognized as an independent risk factor for cardiovascular and cerebrovascular diseases. Hyperhomocysteinemia is reportedly associated with high serum uric acid (sUA) levels. MTHFR C677T polymorphism is assciated with increase in sHcy. Some studies have suggested a positive correlation between MTHFR C677T polymorphism and sUA, but it remains unclear.
Objectives We aimed to evaluate the association between sHcy and sUA as well as MTHFR C677T polymorphism and sUA.
Methods Patients with memory impairment who visited neurology outpatient clinic were enrolled excluding those who were taking medication for the control of hyperuricemia. Hyperuricemia was defined as >7.0 mg/dl for male and >5.6 mg/dl for female. Hyperhomocysteinemia was defined as >15 μmol/l. Clinical laboratory examinations and genotyping for MTHFR C677T polymorphism was performed. Statistical analyses were performed using chi-square, Pearson's correlation coefficients, and ANOVA.
Results Data from 861 subjects (264 male and 597 female) were analyzed. The mean age was 73.2±11.3 years in male and 75.3±10.3 years in female. Male showed significantly higher smoking, alcohol intake, LDL cholesterol, sUA, and sHcy levels, whereas HDL cholesterol, vitamin B12, folic acid were significantly lower compared to female. The prevalence of hyperhomocysteinemia was 38.6% (n=102) in male and 21.4% (n=128) in female. Hyperuricemia was also more common in male with prevalence of 13.3% (n=35) compared to 18.8% (n=112) in female and the mean sUA level was significantly higher in male (5.7±1.4 mg/dl vs 4.6±1.3 mg/dl, p<0.001).
sHcy was significantly associated with both folic acid (r=-0.307, p<0.001) and vitamin B12 (r=-0.197 p<0.001). Subjects with elevated sHcy levels had an odds ratio (OR) of 2.7 (95% CI 1.4–5.4) in male and 2.0 (95% CI 1.4–3.1, p=0.001) in female for hyperuricemia. The genotype frequency of MTHFR C677T was 32.8% (n=282) for CC, 49.8% (n=429) for CT, and 17.4% (n=150) for TT. TT genotype showed association with hyperhomocysteinemia when both gender were analyzed. In male, TT genotype (r=0.399, p=0.007) was associated with positive correlation between hyperhomocysteineima and hyperuricemia. In female, CT (r=0.289, p<0.001) and CC (r=0.240, p<0.001) was associated with positive correlation between hyperhomocysteineima and hyperuricemia. MTHFR C677T polymorphism was not associated with hyperuricemia.
Conclusions Low serum folic acid and vitamin B12 are significant risk factors for hyperhomocysteinema, which reflects the influence of alcohol consumption and vitamin deficiencies on sHcy level. TT genotype of the MTHFR C677T was associated with hyperhomocysteinemia.
A positive association was observed between sHcy levels and sUA levels for both males and females which is in agreement with previous studies. Male having the TT genotype and female having the CT and CC genotype with hyperhomocysteinemia are likely to have higher sUA level.
MTHFR C677T polymorphism is not associated with sUA level, which is inconsistent with recent studies.
Assessment of a possible link between hyperhomocysteinemia and hyperuricemia. Eytan Cohen, et al. J Investig Med 2015;63: 534–538.
Meta-analysis of the association of the C677T polymorphism of the methylenetetrahydrofolate reductase gene with hyperuricemia. Wen wei, et al. Ann Nutr Metab 2012;60:44–51.
Disclosure of Interest None declared