MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine concentrations

Department of Food Science and Nutrition, Zhejiang University, Hangzhou 310029, China.
Nutrition, metabolism, and cardiovascular diseases: NMCD (Impact Factor: 3.32). 12/2010; 22(4):362-8. DOI: 10.1016/j.numecd.2010.07.015
Source: PubMed


Dietary n-3 polyunsaturated fatty acids (PUFAs) are associated with decreased plasma homocysteine (Hcy), an important biomarker for cardiovascular disease. The S-adenosylmethionine synthetase type-1 (MAT1A), an essential enzyme in the conversion of methionine to S-adenosylmethionine, plays a key role in homocysteine metabolism. This study investigated the interaction between dietary fatty acids and MAT1A genotypes on plasma Hcy concentrations among Boston Puerto Ricans.
Plasma Hcy and MAT1A genotypes were determined in 994 subjects of the Boston Puerto Rican Health Study. Dietary fatty acid intakes were assessed by interviews using a questionnaire adapted from the NCI/Block food frequency form.
In the cross-sectional analysis, genetic variant MAT1A 3U1510 displayed a significant interaction with dietary n-3:n-6 PUFA ratio in determining plasma Hcy (p-value for interaction = 0.025). 3U1510G homozygotes had significantly lower plasma Hcy concentration than major allele homozygotes and heterozygotes (AA + AG) (p-value for trend = 0.019) when the n-3:n-6 ratio was >0.09. Two other MAT1A variants, d18777 and i15752, also showed significant interactions with different constituents of dietary fat influencing Hcy concentrations. Furthermore, haplotypes consisting of three variants displayed a strong interaction with n3:n6 ratio influencing Hcy concentrations.
Our results suggest that MAT1A genotypes appear to modulate effects of dietary fat on plasma Hcy.

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    • "Our animal study suggested that 22:6í µí±›-3 decreases plasma Hcy concentration through regulating critical gene expression and enzyme activity [12]. Our population studies found that dietary fatty acids interact with methylenetetrahydrofolate reductase (MTHFR) and methionine adenosyltransferase I, alpha (MAT1A) genetic variants in determining plasma Hcy concentration [13] [14]. Recently an intervention study also demonstrated that consumption of í µí±›-3 PUFA supplements (3 g/day) for 2 months decreases the levels of Hcy in those with type 2 diabetes mellitus [15]. "
    DUO LI ·
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    ABSTRACT: The objective was to investigate the regulatory effect of polyunsaturated fatty acids (PUFAs) on mRNA expression of key genes involved in homocysteine (Hcy) metabolism. Eighty male Sprague Dawley rats were randomly divided into eight groups. The oils were orally administered daily for 8 weeks. Plasma Hcy, phospholipids fatty acids, and mRNA expression were determined. Compared with the control group, plasmaHcywas significantly decreased in the 22:6n-3 and conjugated linoleic acid (CLA) groups; mRNA expression of Mthfr was significantly upregulated in the 22:6n-3, 20:5n-3, and 18:3n-3 groups and downregulated in the 18:2n-6 and stearolic acid (SO) groups. Mat1a was upregulated in the 22:6n-3, 20:5n-3, 18:3n-3, and CLA groups. In addition, Cbs was upregulated in the 22:6n-3, 20:5n-3, 18:3n-3 and CLA groups while downregulated in 18:2n-6 and SO groups. Dietary 22:6n-3 and CLA decrease the plasma concentration of Hcy. mRNA expression of Mthfr, Mat1a, Cbs and Pemt, Gnmt, Mtrr, and Bad is upregulated by n-3 PUFA and downregulated by n-6 PUFA. CLA upregulates mRNA expression of Mat1a and Cbs.
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    • "The findings of these studies, however, may be limited due to a lack of adjustment for folate [18,20,21], vitamin B6 [17-21], vitamin B12 [18,20,21], physical activity [17-21] and smoking status [18-21], all of which are important determinants of homocysteine concentrations [22]. As regards the association between homocysteine and n-6 PUFAs, which have also been linked to a lower risk for cardiovascular disease if supplemented in combination with n-3 PUFAs [23], a few studies with blood fatty acid measurement showed inconsistent results [19,20,24]. "
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    ABSTRACT: Supplementation studies have suggested a role of n-3 polyunsaturated fatty acids (PUFAs) in homocysteine metabolism, but the evidence is limited and inconsistent among studies that measured blood levels of n-3 and n-6 PUFAs. We examined the association between blood levels of PUFAs and homocysteine in Japanese men and women. The subjects were 496 employees (290 men and 206 women) of 2 municipal offices in Japan. Fatty acid composition in serum phospholipids and cholesterol ester (CE) was measured using gas-liquid chromatography. Multiple regression was used to calculate means of homocysteine concentrations according to PUFA tertile with adjustment for potential confounders. Serum homocysteine concentration decreased with increasing levels of total n-3 PUFA, eicosapentaenoic acid and docosahexaenoic acid (DHA) in serum phospholipids and CE with adjustment for age, sex and workplace. However, only DHA in serum phospholipids remained statistically significant after additional adjustment for other potential confounders including serum folate (P-trend = 0.04). N-6 PUFAs were not significantly associated with homocysteine concentrations. Higher proportion of DHA in serum phospholipids may be associated with lower homocysteine concentrations in Japanese men and women.
    Nutrition & Metabolism 06/2013; 10(1):41. DOI:10.1186/1743-7075-10-41 · 3.26 Impact Factor
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    • "Variations in the levels of Hcy can be due to defects of the genes encoding the critical enzymes involved in methionine metabolism [6], nutritional status for folic acid, vitamin B6 and B12, and various personal behaviours like physical inactivity and smoking [7]. Hcy metabolism is nutritionally regulated in part through the utilization of Hcy in the transsulfuration and remethylation pathways [8]. "
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    ABSTRACT: Previous studies showed that plasma n-3 polyunsaturated fatty acid (PUFA) was negatively associated with plasma homocysteine (Hcy). We investigated the regulatory effect of n-3 PUFA on mRNA expression of the critical genes encoding the enzymes involved in Hcy metabolism. HepG2 cells were treated with docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA) respectively for 48 h. The cells were collected and total RNA was isolated. The mRNA expression levels of the genes were determined by using Real Time-PCR. Compared with controls, the mRNA expression levels of 5-methyltetrahydrofolate reductase (MTHFR) were significantly increased in the DHA group (p < 0.05) and ALA group (p < 0.05); Significantly down-regulated mRNA expression of methionine adenosyltransferase (MAT) was observed with the treatments compared with the controls; the level of MAT expression was significant lower in the DHA group than the ALA group (p < 0.05); Cystathionine-γ-lyase (CSE) expression was significantly increased in the DHA (p < 0.05) and EPA groups (p < 0.05) compared with control. No significant changes were shown in mRNA expression levels of S-adenosylhomocysteine hydrolases (SAHH), cystathionine β-synthase (CBS), and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Our results suggest that DHA up-regulates CSE and MTHFR mRNA expression and down-regulates MAT mRNA expression involved in Hcy metabolism.
    Nutrition Journal 01/2012; 11(1, article 6):6. DOI:10.1186/1475-2891-11-6 · 2.60 Impact Factor
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