C677T Mutation in the MTHFR Gene Increases Serum Uric Acid in Obese Subjects. : Posters IX

C677T Mutation in the Methylenetetrahydrofolate Reductase Gene Increases Serum Uric Acid in Obese Subjects

http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2010.PART1.P9.P1-448

June 19, 2010

Abstract:

Methylenetetrahydrofolate reductase (MTHFR) is a regulatory enzyme in the remethylation phase of homocysteine metabolism. A common mutation of MTHFR gene (C-to T transition at nucleotide position 677) has been reported as a genetic risk factor for hyperhomocysteinemia, cardiovascular disease. Recently Zuo et al. and Itou et al. reported that C677T mutation in the MTHFR gene contributed to higher uric acid levels. 

Furthermore, Lambrinoudaki et al. reported that the mutation has been associated with central adiposity in healthy postmenopausal women. Since obesity is a risk factor for hyperuricemia, determining whether obese subjects have C677T mutation of the MTHFR gene is important. To investigate whether the C677T MTHFR mutation is a risk factor for hyperuricemia in obese subjects, we performed MTHFR genotyping analysis and clinical laboratory determinations including serum uric acid in obese Japanese subjects. 

We studied 141 obese Japanese who consulted the outpatient clinic of our hospital for treatment of their condition. Obesity was diagnosed according to the criteria of the Japan Society for the Study of Obesity. The control group was comprised of 146 age-matched healthy people who consulted Sakazaki Clinic for a routine medical examination. Blood samples were drawn after an overnight fast. Serum uric acid, creatinine and total cholesterol were determined by standard enzymatic methods. Genomyc DNA was extracted from peripheral blood leukocytes. 

The genotype of SNP 677 of the MTHFR was determined with a fluorescent allele-specific DNA primer assay system. Distribution of the MTHFR genotypes was CC, 38%; TC,39%; TT,23%; with a T-allele frequency 0.42 in obese subjects, and CC, 39%; TC, 52%; TT,9%; with a T-allele frequency 0.36 in the controls. T-allele frequency was higher among obese subjects than among control subjects. 

There is a significant association between MTHFR polymorphism and levels of uric acid (CC 5.3±1.2mg/dl, CT/TT 5.9±1.2 mg/dl). There were no differences between MTHFR polymorphisms and creatinine, cholesterol and blood pressure. Subjects were classified into two groups based on uric acid levels; a low uric acid group (< 7.0 mg/dl) and a high uric acid group (≥ 7.0 mg/dl). T allele frequency was significantly greater in the high uric acid group than in the low uric acid group. In this study, the C677T MTHFR mutation is associated with hyperuricemia in obese subjects. People with this mutation should be careful to avoid a high-purine diet.