The MTHFR C677T Polymorphism and Hyperuricemia Risk: a Meta-analysis of 558 Cases and 912 Controls

Abstract

Both genetic and environmental factors play roles in hyperuricemia and susceptibility may be modified by functional polymorphisms in folate metabolic genes, such as methylenetetrahydrofolate reductase (MTHFR). Several case control studies investigated association between C677T polymorphism with hyperuricemia but the sample size was small in these studies and the association power was weak. The aim of the present meta-analysis was to evaluate association between MTHFR C677T polymorphism and hyperuricemia. This meta-analysis recruited 6 published studies which were selected by search of electronic databases up to August 2013, including 558 hyperuricemic cases and 912 healthy controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR C677T polymorphism and hypeuricemia susceptibility using fixed effect models. Statistically significant relationship was found between C677T polymorphism and hyperuricemia with all genetic models (Additive model T vs. C: OR=1.

Hyper-homocysteinemia Inducing Hyperuricemia: What are the Mechanisms?

“…Concordantly, 10-formyl-tetrahydrofolate acts as a donor of formyl groups for the biosynthesis of purines, that induce an increase of UA concentration [27]. But, a disagreement still exists about the relationship between the MTHFR C667T polymorphism and increased UA levels In fact, several authors described that MTHFR C677T polymorphism may be a risk factor for hyperuricemia [22][23][24][25][26][27][28][29][30]. In addition, recently two meta-analyses further confirmed this association [27][28][29][30][31].…”

“…MTHFR is a main regulator enzyme able to catalyzes the reduction of 5,10-methylene-tetra-hydrofolate to 5-methyl-tetra-hydrofolate, which acts as the carbon donor in the remethylation of homocysteine to methionine. Although the mechanisms of the relationship between MTHFR C677T polymorphism and serum UA is still unknown, it can be hypothesized that this MTHFR gene mutation could favor de novo synthesis of purines via 10-formyl-tetrahydrofolate, resulting in increased production of UA [26]. Concordantly, 10-formyl-tetrahydrofolate acts as a donor of formyl groups for the biosynthesis of purines, that induce an increase of UA concentration [27].…”

Maternal MTHFR A1298C polymorphism and risk of congenital heart disease in fetus

“…Meta-analysis is a statistical tool which is successfully used for combining results of several small, low powered case control studies to conclude the results with less statistical error and high statistical power. Numerous meta- analyses were published to confirm the small effect of gene polymorphism as risk factor for several disease like- cleft lip and palate (Rai,2014a,2018b); NTD (Yadav et al, 2015); male infertility (Rai and Kumar,2017d), Down syndrome (Rai,2011a; Rai et al,2017c; Rai and Kumar,2018a); recurrent pregnancy loss (Rai,2016a), glucose 6- phosphate dehydrogenase deficiency (Kumar et al,2016), bipolar disorder (Rai,2011b), Schizophrenia(Yadav et al2016a, Rai et al,2017e), autism (Rai,2016c; Rai and Kumar,2018c), Depression (Rai,2014c); Alzheimers disease (Rai,2016b,2017a); epilepsy (Rai and Kumar, 2018d), Uterine Leiomyoma (Kumar and Rai, 2018a), hyperurecemia (Rai,2016d), breast cancer (Rai,2014b; Rai et al,2017b), esophageal cancer (Kumar and Rai, 2018b), lung cancer (Rai,2014d), prostate cancer (Yadav et al,2016b),colorectal cancer (Rai,2015), digestive tract cancer (Yadav et al,2018), endometrial cancer (Kumar and Rai, 2018c) and ovary cancer (Rai,2016e).…”