Nutrigenetic influence of MTHFR (C677T) variants on folate metabolism in systemic lupus erythematosus

IF 0.3 Q4 NUTRITION & DIETETICS

CAHIERS DE NUTRITION ET DE DIETETIQUE Pub Date : 2026-08-01 Epub Date: 2026-09-24 DOI:10.1016/j.cnd.2026.08.078

Lucas Moura Carvalho, Jhulia Caroline Nunes Leal da Mota, Amanda Alves Ribeiro, Beatriz Garcia Carvalho, Bruno Gualano, Jose Alfredo Martínez, Eduardo Ferreira Borba, Carolina Nicoletti Ferreira Fino

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In this context, polymorphisms in genes related to folate metabolism, such as methylenetetrahydrofolate reductase (MTHFR), may influence the availability of essential micronutrients, including folic acid, thereby affecting DNA methylation processes and immune cell function. However, the association between MTHFR (C677T) genetic variants and metabolic and nutritional biomarkers in SLE remains poorly understood.</div></div><div>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation, systemic inflammation, and high clinical heterogeneity. Emerging evidence suggests that alterations in one-carbon metabolism play a relevant role in immune homeostasis and epigenetic regulation involved in SLE pathophysiology. In this context, polymorphisms in genes related to folate metabolism, such as methylenetetrahydrofolate reductase (MTHFR), may influence the availability of essential micronutrients, including folic acid, thereby affecting DNA methylation processes and immune cell function. However, the association between MTHFR (C677T) genetic variants and metabolic and nutritional biomarkers in SLE remains poorly understood.</div><div><h3>Objective</h3><div>To investigate the association between the <em>MTHFR</em> (<em>C677T</em>) gene polymorphism and serum folic acid levels in patients with systemic lupus erythematosus.</div></div><div>To investigate the association between the <em>MTHFR</em> (<em>C677T</em>) gene polymorphism and serum folic acid levels in patients with systemic lupus erythematosus.</div><div><h3>Methods</h3><div>A cross-sectional study (CAAE.: 86418824.6.0000.0068) was conducted including 100 women with SLE (18–45 years). Peripheral blood samples were collected for genetic and biochemical analyses. Genotyping of the MTHFR rs1801133 (C677T) polymorphism was performed using real-time polymerase chain reaction (qPCR) with TaqMan SNP genotyping assays. Genetic associations were evaluated under dominant (CC vs. CT+TT) and recessive (CC+CT vs. TT) inheritance models. Serum folate levels were measured and used as the dependent variable. The association between genotype and folate concentrations was assessed using linear regression analysis, with statistical significance set at <em>P</em>      <0.05.</div><div><h3>Results</h3><div>The genotype distribution showed 33% (<em>n</em>  =67) for CT+TT under the dominant model. Under the recessive model, 82% (<em>n</em>    =18) carried TT. A significant association was observed between the recessive model of MTHFR and serum folate levels. The regression model showed R2=0.113 with statistical significance (<em>P</em>    =0.013).</div></div><div>The genotype distribution showed 33% (<em>n</em>  =67) for CT+TT under the dominant model. Under the recessive model, 82% (<em>n</em>    =18) carried TT. A significant association was observed between the recessive model of MTHFR and serum folate levels. The regression model showed R2=0.113 with statistical significance (<em>P</em>    =0.013).</div><div><h3>Conclusion</h3><div>MTHFR C677T recessive variants are associated with reduced serum folic acid levels in SLE patients. These findings highlight the role of one-carbon metabolism in SLE and support the relevance of nutrigenetic interactions in disease-related metabolic alterations.</div></div><div>MTHFR C677T recessive variants are associated with reduced serum folic acid levels in SLE patients. 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引用次数: 0

Abstract

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation, systemic inflammation, and high clinical heterogeneity. Emerging evidence suggests that alterations in one-carbon metabolism play a relevant role in immune homeostasis and epigenetic regulation involved in SLE pathophysiology. In this context, polymorphisms in genes related to folate metabolism, such as methylenetetrahydrofolate reductase (MTHFR), may influence the availability of essential micronutrients, including folic acid, thereby affecting DNA methylation processes and immune cell function. However, the association between MTHFR (C677T) genetic variants and metabolic and nutritional biomarkers in SLE remains poorly understood.

Objective

To investigate the association between the MTHFR (C677T) gene polymorphism and serum folic acid levels in patients with systemic lupus erythematosus.

Methods

A cross-sectional study (CAAE.: 86418824.6.0000.0068) was conducted including 100 women with SLE (18–45 years). Peripheral blood samples were collected for genetic and biochemical analyses. Genotyping of the MTHFR rs1801133 (C677T) polymorphism was performed using real-time polymerase chain reaction (qPCR) with TaqMan SNP genotyping assays. Genetic associations were evaluated under dominant (CC vs. CT + TT) and recessive (CC + CT vs. TT) inheritance models. Serum folate levels were measured and used as the dependent variable. The association between genotype and folate concentrations was assessed using linear regression analysis, with statistical significance set at P < 0.05.

Results

The genotype distribution showed 33% (n = 33) for CC and 67% (n = 67) for CT + TT under the dominant model. Under the recessive model, 82% (n = 82) carried CC + CT and 18% (n = 18) carried TT. A significant association was observed between the recessive model of MTHFR and serum folate levels. The regression model showed R2 = 0.113 with statistical significance (P = 0.017). Individuals carrying the TT genotype presented lower serum folate concentrations compared to other genotypes (β = −3.28; P = 0.013).

Conclusion

MTHFR C677T recessive variants are associated with reduced serum folic acid levels in SLE patients. These findings highlight the role of one-carbon metabolism in SLE and support the relevance of nutrigenetic interactions in disease-related metabolic alterations.

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MTHFR （C677T）变异对系统性红斑狼疮患者叶酸代谢的营养遗传学影响

系统性红斑狼疮（SLE）是一种以免疫失调、全身性炎症和高度临床异质性为特征的慢性自身免疫性疾病。新出现的证据表明，单碳代谢的改变在SLE病理生理的免疫稳态和表观遗传调节中起着相关作用。在这种情况下，与叶酸代谢相关的基因多态性，如亚甲基四氢叶酸还原酶（MTHFR），可能影响必需微量营养素（包括叶酸）的可用性，从而影响DNA甲基化过程和免疫细胞功能。然而，MTHFR （C677T）遗传变异与SLE代谢和营养生物标志物之间的关系仍知之甚少。系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，以免疫失调、全身性炎症和高临床异质性为特征。新出现的证据表明，单碳代谢的改变在SLE病理生理的免疫稳态和表观遗传调节中起着相关作用。在这种情况下，与叶酸代谢相关的基因多态性，如亚甲基四氢叶酸还原酶（MTHFR），可能影响必需微量营养素（包括叶酸）的可用性，从而影响DNA甲基化过程和免疫细胞功能。然而，MTHFR （C677T）遗传变异与SLE代谢和营养生物标志物之间的关系仍知之甚少。目的探讨系统性红斑狼疮患者MTHFR （C677T）基因多态性与血清叶酸水平的关系。探讨系统性红斑狼疮患者MTHFR （C677T）基因多态性与血清叶酸水平的关系。方法采用横断面研究（CAAE）。： 86418824.6.0000.0068)纳入100例SLE女性（18-45岁）。采集外周血进行遗传和生化分析。采用实时聚合酶链反应（qPCR）和TaqMan SNP基因分型技术对MTHFR rs1801133 （C677T）多态性进行基因分型。在显性遗传模型（CC vs. CT + TT）和隐性遗传模型（CC + CT vs. TT）下评估遗传关联。测定血清叶酸水平并将其作为因变量。采用线性回归分析评估基因型与叶酸浓度的相关性，P <； 0.05为有统计学意义。横断面研究（CAAE）。： 86418824.6.0000.0068)纳入100例SLE女性（18-45岁）。采集外周血进行遗传和生化分析。采用实时聚合酶链反应（qPCR）和TaqMan SNP基因分型技术对MTHFR rs1801133 （C677T）多态性进行基因分型。在显性遗传模型（CC vs. CT + TT）和隐性遗传模型（CC + CT vs. TT）下评估遗传关联。测定血清叶酸水平并将其作为因变量。采用线性回归分析评估基因型与叶酸浓度的相关性，P <； 0.05为有统计学意义。结果优势模型下CC基因型分布为33% (n = 33)， CT + TT基因型分布为67% （n = 67）。隐性模型下，82% （n = 82）携带CC + CT， 18% （n = 18）携带TT。MTHFR的隐性模型与血清叶酸水平显著相关。回归模型显示R2 = 0.113，差异有统计学意义（P = 0.017）。携带TT基因型的个体血清叶酸浓度低于其他基因型（β = - 3.28; P = 0.013）。优势模型下CC和CT + TT的基因型分布分别为33% （n = 33）和67% （n = 67）。隐性模型下，82% （n = 82）携带CC + CT， 18% （n = 18）携带TT。MTHFR的隐性模型与血清叶酸水平显著相关。回归模型显示R2 = 0.113，差异有统计学意义（P = 0.017）。携带TT基因型的个体血清叶酸浓度低于其他基因型（β = - 3.28; P = 0.013）。结论mthfr C677T隐性变异与SLE患者血清叶酸水平降低相关。这些发现强调了单碳代谢在SLE中的作用，并支持营养与遗传相互作用在疾病相关代谢改变中的相关性。MTHFR C677T隐性变异与SLE患者血清叶酸水平降低相关。这些发现强调了单碳代谢在SLE中的作用，并支持营养与遗传相互作用在疾病相关代谢改变中的相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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CAHIERS DE NUTRITION ET DE DIETETIQUE NUTRITION & DIETETICS-

CiteScore

0.60

自引率

33.30%

发文量

审稿时长

65 days

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