The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment.

Young Seo Kim,Jae-Bum Jun,Il Woong Sohn,Hee-Jin Kim

doi:10.3390/nu12041147

Abstract

In an elderly population with cognitive impairment, we investigated the association between serum uric acid (sUA) and serum homocysteine (sHcy), known risk factors for cerebrovascular disease. We also investigated the potential effect of the C677T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) to the sUA level in different dementia types. Participants underwent a battery of tests including measurements of sUA, sHcy, folic acid, and vitamin B12 as well as genotyping of the MTHFR locus. Data from 861 subjects (597 females to 264 males) were retrospectively analyzed. Subjects with hyperhomocysteinemia had lower serum folic acid and vitamin B12 and higher sUA than those with normal sHcy. sUA was significantly associated with serum creatinine, HbA1c, and sHcy regardless of gender. The TT genotype was found to be associated with hyperhomocysteinemia in both genders (p = 0.001). The levels of hyperlipidemia, sHcy, and sUA differed according to dementia subtypes. High sUA were associated with hyperhomocystenemia in TT genotype only in dementia with vascular lesion. This study reveals that sUA is positively associated with sHcy. We speculate that the two markers synergistically increase cerebrovascular burden and suggested that dietary intervention for sUA and sHcy would be helpful for cognitive decline with vascular lesion.

Highlights

Serum uric acid level is associated with gout, hypertension, cardiovascular disease, renal insufficiency, and metabolic syndrome [1,2]
Utilizing the available data from a neurology-based outpatient memory clinic, we aimed to investigate the association between Serum uric acid (sUA) and serum homocysteine (sHcy), as well as the potential effect of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on the sUA and sHcy levels, and on vascular disease outcomes in cognitive impaired elderly patients
We postulated that MTHFR mutation results in elevated sHcy levels and high sUA levels, and they were positively associated with metabolic risk factors

Summary

Introduction

Serum uric acid (sUA) level is associated with gout, hypertension, cardiovascular disease, renal insufficiency, and metabolic syndrome [1,2]. Recent studies have shown a positive correlation between sUA and sHcy [17]. Both sUA and sHcy levels might be complex outcomes influenced by multiple genetic and environmental factors. MTHFR mutations are candidates as important genetic influences on sUA, and recent genome-wide association studies have detected genetic variants related to sUA levels [20,22]. The MTHFR genetic variant C677T was reported as a probable independent risk factor for hyperuricemia in a meta-analysis [20,23]

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