Hyperhomocysteinemia in Takayasu arteritis—genetically defined or burden of the proinflammatory state?
Takayasu arteritis (TAK) is associated with high plasma homocysteine (Hcy) and elevated Hcy predicts ischemic events. Thus, this study aims to compare the frequency of single-nucleotide polymorphisms (SNPs) of genes involved in Hcy metabolism between TAK and controls and analyze associations with Hc...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574479/full |
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| author | Eduarda Bonelli Zarur Eduarda Bonelli Zarur Faustino Peron Filho Allan Chiaratti de Oliveira Gerson Dierley Keppeke Gerson Dierley Keppeke Vânia D’Almeida Alexandre Wagner Silva de Souza |
| author_facet | Eduarda Bonelli Zarur Eduarda Bonelli Zarur Faustino Peron Filho Allan Chiaratti de Oliveira Gerson Dierley Keppeke Gerson Dierley Keppeke Vânia D’Almeida Alexandre Wagner Silva de Souza |
| author_sort | Eduarda Bonelli Zarur |
| collection | DOAJ |
| description | Takayasu arteritis (TAK) is associated with high plasma homocysteine (Hcy) and elevated Hcy predicts ischemic events. Thus, this study aims to compare the frequency of single-nucleotide polymorphisms (SNPs) of genes involved in Hcy metabolism between TAK and controls and analyze associations with Hcy levels, TAK features, and acute ischemic arterial events (AIAEs). A cross-sectional study was performed with 73 TAK patients and 71 controls. SNPs of genes involved in the Hcy metabolism, plasma Hcy, and risk factors were analyzed for hyperhomocysteinemia (HHcy), cardiovascular disease (CVD), and AIAEs. Patients presented a higher frequency of risk factors for CVD and HHcy. At least one AIAE was observed in 27 (37.0%) patients and one control. The frequency of the SNPs was similar between both groups, and there was no association between SNP carriage and AIAEs. TAK patients presented higher Hcy levels than controls (13.9 ± 5.6 µmol/L vs. 8.6 ± 4.0 µmol/L; p < 0.001), and patients carrying MTHFR677TT presented higher Hcy levels than those carrying MTHFR677CT (20.4 ± 7.8 µmol/L vs. 13.7 ± 5.2 µmol/L; p = 0.02) or MTHFR677CC (20.4 ± 7.8 µmol/L vs. 13.1 ± 4.7 µmol/L; p = 0.009). TAK was an independent risk factor for HHcy [odds ratio (OR) = 10.20; 95% confidence interval (95% CI): 4.16–25.00; p < 0.001], and in TAK, thiazide diuretic use was a risk factor for HHcy (OR = 11.61; 95% CI: 1.63–82.63; p < 0.01). In conclusion, TAK was a risk factor for HHcy but not related to SNPs in genes encoding Hcy metabolism enzymes. The burden of chronic inflammation and thiazide diuretics contribute to HHcy in TAK. |
| format | Article |
| id | doaj-art-72df84c873ee4961a2bfb542dab35492 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-72df84c873ee4961a2bfb542dab354922025-08-20T03:05:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15744791574479Hyperhomocysteinemia in Takayasu arteritis—genetically defined or burden of the proinflammatory state?Eduarda Bonelli Zarur0Eduarda Bonelli Zarur1Faustino Peron Filho2Allan Chiaratti de Oliveira3Gerson Dierley Keppeke4Gerson Dierley Keppeke5Vânia D’Almeida6Alexandre Wagner Silva de Souza7Rheumatology Division, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, BrazilRheumatology Division, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, BrazilRheumatology Division, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, BrazilDepartment of Pediatrics, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilRheumatology Division, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, BrazilDepartamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, ChileDepartment of Psychobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilRheumatology Division, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, BrazilTakayasu arteritis (TAK) is associated with high plasma homocysteine (Hcy) and elevated Hcy predicts ischemic events. Thus, this study aims to compare the frequency of single-nucleotide polymorphisms (SNPs) of genes involved in Hcy metabolism between TAK and controls and analyze associations with Hcy levels, TAK features, and acute ischemic arterial events (AIAEs). A cross-sectional study was performed with 73 TAK patients and 71 controls. SNPs of genes involved in the Hcy metabolism, plasma Hcy, and risk factors were analyzed for hyperhomocysteinemia (HHcy), cardiovascular disease (CVD), and AIAEs. Patients presented a higher frequency of risk factors for CVD and HHcy. At least one AIAE was observed in 27 (37.0%) patients and one control. The frequency of the SNPs was similar between both groups, and there was no association between SNP carriage and AIAEs. TAK patients presented higher Hcy levels than controls (13.9 ± 5.6 µmol/L vs. 8.6 ± 4.0 µmol/L; p < 0.001), and patients carrying MTHFR677TT presented higher Hcy levels than those carrying MTHFR677CT (20.4 ± 7.8 µmol/L vs. 13.7 ± 5.2 µmol/L; p = 0.02) or MTHFR677CC (20.4 ± 7.8 µmol/L vs. 13.1 ± 4.7 µmol/L; p = 0.009). TAK was an independent risk factor for HHcy [odds ratio (OR) = 10.20; 95% confidence interval (95% CI): 4.16–25.00; p < 0.001], and in TAK, thiazide diuretic use was a risk factor for HHcy (OR = 11.61; 95% CI: 1.63–82.63; p < 0.01). In conclusion, TAK was a risk factor for HHcy but not related to SNPs in genes encoding Hcy metabolism enzymes. The burden of chronic inflammation and thiazide diuretics contribute to HHcy in TAK.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574479/fullTakayasu Arteritishyperhomocysteinemiacardiovascular diseasearterial inflammationsingle nucleotide polymorphismhomocysteine |
| spellingShingle | Eduarda Bonelli Zarur Eduarda Bonelli Zarur Faustino Peron Filho Allan Chiaratti de Oliveira Gerson Dierley Keppeke Gerson Dierley Keppeke Vânia D’Almeida Alexandre Wagner Silva de Souza Hyperhomocysteinemia in Takayasu arteritis—genetically defined or burden of the proinflammatory state? Frontiers in Immunology Takayasu Arteritis hyperhomocysteinemia cardiovascular disease arterial inflammation single nucleotide polymorphism homocysteine |
| title | Hyperhomocysteinemia in Takayasu arteritis—genetically defined or burden of the proinflammatory state? |
| title_full | Hyperhomocysteinemia in Takayasu arteritis—genetically defined or burden of the proinflammatory state? |
| title_fullStr | Hyperhomocysteinemia in Takayasu arteritis—genetically defined or burden of the proinflammatory state? |
| title_full_unstemmed | Hyperhomocysteinemia in Takayasu arteritis—genetically defined or burden of the proinflammatory state? |
| title_short | Hyperhomocysteinemia in Takayasu arteritis—genetically defined or burden of the proinflammatory state? |
| title_sort | hyperhomocysteinemia in takayasu arteritis genetically defined or burden of the proinflammatory state |
| topic | Takayasu Arteritis hyperhomocysteinemia cardiovascular disease arterial inflammation single nucleotide polymorphism homocysteine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1574479/full |
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