Objective: In this study, we investigated whether methionine synthase (MTR) A2756G and methionine synthase reductase
(MTRR) A66G gene polymorphisms were related with infertility.
The genes they have looked at are involved in the intracellular transport (reduced folate carrier 1 or RFC1), and conversion ([gamma] glutamyl hydrolase or GGH) of methotrxate, metabolism of purine and pyrimidine (methylenetetrahydrofolate reductase or MTHFR, thymidylate synthase or TS, methionine synthase or MS, serine hydroxymethyltransferase I or SHMT 1 , aminoimidazol carboxamide ribinucleotide transformylase or ATIC, methionine synthase reductase
or MTRR) and efflux of the drug (multidrug resistance protein 1 or MDR1).
The functional deficiency depends on mutations in the methionine synthase gene or in the gene encoding methionine synthase reductase
, an enzyme involved in the reductive activation of methionine synthase (Leclerc et al, 1998).
7) Another, more recent patent, also filed in 1999 and awarded May 1, 2006, is for the methods by which methionine synthase reductase
, which is in the same pathway as MTHFR and is also a cause of hyperhomocysteinemia.
Transcobalamin and methionine synthase reductase
mutated polymorphisms aggravate the risk of neural tube defects in humans.
The first is the lack of information about the methionine synthase A2756G and methionine synthase reductase
A66G polymorphisms involved in methionine metabolism.
The genes analyzed were MTHFR: Methylenetetrahydrofoate reductase; TS: Thymidylate synthase; RFC1: Reduce folatecarrier1 ;MS: Methionine synthase; SHMT1: Serine hydroxymethyltransferase1; MDR1: Multidrug resistantprotein1; GGH: [gamma] glutamyl hydrolase; ATIC: Aminoimidazol carboxamide ribonucleotide transformylase; MTRR: Methionine synthase reductase
In addition to MTHFR C677T polymorphism, other polymorphisms in MTHFR and other genes in the pathway, namely, methionine synthase (MTR), cystathionine-beta-synthase and methionine synthase reductase
(MTRR) are being studied knowing the polygenic aetiology of hypermethionemia and CAD (21,22).
Hyperhomocysteinemia is caused by low intake of folate and other B vitamins and by genetic factors (6, 7), including polymorphisms of genes encoding enzymes involved in Hcy remethylation, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase
(MTRR), and variants of cystathionine [beta]-synthase (CBS), which catalyzes the irreversible step of the transsulfuration pathway (Fig.
c) Homocystinuria includes deficiency in CBS, MTHFR, methionine synthase, or methionine synthase reductase
and defects in intracellular cobalamin metabolism (see Fig.
These SNPs include methylenetetrahydrofolate (MTHFR) C677T (1), MTHFR A1298C (4), methionine synthase (MTR) A2756G (5, 6), and methionine synthase reductase
(MTRR) A66G (7).
Both flavin coenzymes are involved in cobalamin metabolism (12 ) and serve as cofactors for methionine synthase reductase