MTHFR 677C>T (rsRS1801133) variant is associated with hyperhomocysteinemia but not with clinical severity in patients with peripheral arterial disease.
Guilherme da Silva Silvestre, Iriana Moratto Carrara, Tamires Flauzino, Marcell Alysson Batisti Lozovoy, Rubens Cecchini, Edna Maria Vissoci Reiche, Andréa Name Colado Simão
{"title":"<i>MTHFR</i> 677C>T (rsRS1801133) variant is associated with hyperhomocysteinemia but not with clinical severity in patients with peripheral arterial disease.","authors":"Guilherme da Silva Silvestre, Iriana Moratto Carrara, Tamires Flauzino, Marcell Alysson Batisti Lozovoy, Rubens Cecchini, Edna Maria Vissoci Reiche, Andréa Name Colado Simão","doi":"10.1590/1677-5449.202200612","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The <i>MTHFR</i> 677C>T variant's involvement with hyperhomocysteinemia and peripheral arterial disease (PAD) is still unclear.</p><p><strong>Objectives: </strong>To evaluate associations between the <i>MTHFR</i> 677C>T (rs1801133) variant and susceptibility to and severity of PAD and homocysteine (Hcy) levels.</p><p><strong>Methods: </strong>The study enrolled 157 PAD patients and 113 unrelated controls. PAD severity and anatomoradiological categories were assessed using the Fontaine classification and the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC), respectively. The variant was genotyped using real-time polymerase chain reaction and Hcy levels were determined using chemiluminescence microparticle assay.</p><p><strong>Results: </strong>The sample of PAD patients comprised 60 (38.2%) females and 97 (61.8%) males. Patients were older and had higher Hcy than controls (median age of 69 vs. 45 years, p<0.001; and 13.66 µmol/L vs. 9.91 µmol/L, p=0.020, respectively). Hcy levels and the <i>MTHFR</i> 677C>T variant did not differ according to Fontaine or TASC categories. However, Hcy was higher in patients with the CT+TT genotypes than in those with the CC genotype (14.60 µmol/L vs. 12.94 µmol/L, p=0.008). Moreover, patients with the TT genotype had higher Hcy than those with the CC+CT genotypes (16.40 µmol/L vs. 13.22 µmol/L, p=0.019), independently of the major confounding variables.</p><p><strong>Conclusions: </strong>The T allele of <i>MTHFR</i> 677C>T variant was associated with higher Hcy levels in PAD patients, but not in controls, suggesting a possible interaction between the <i>MTHFR</i> 677C>T variant and other genetic, epigenetic, or environmental factors associated with PAD, affecting modulation of Hcy metabolism.</p>","PeriodicalId":14814,"journal":{"name":"Jornal Vascular Brasileiro","volume":null,"pages":null},"PeriodicalIF":0.8000,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10706007/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jornal Vascular Brasileiro","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1590/1677-5449.202200612","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The MTHFR 677C>T variant's involvement with hyperhomocysteinemia and peripheral arterial disease (PAD) is still unclear.
Objectives: To evaluate associations between the MTHFR 677C>T (rs1801133) variant and susceptibility to and severity of PAD and homocysteine (Hcy) levels.
Methods: The study enrolled 157 PAD patients and 113 unrelated controls. PAD severity and anatomoradiological categories were assessed using the Fontaine classification and the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC), respectively. The variant was genotyped using real-time polymerase chain reaction and Hcy levels were determined using chemiluminescence microparticle assay.
Results: The sample of PAD patients comprised 60 (38.2%) females and 97 (61.8%) males. Patients were older and had higher Hcy than controls (median age of 69 vs. 45 years, p<0.001; and 13.66 µmol/L vs. 9.91 µmol/L, p=0.020, respectively). Hcy levels and the MTHFR 677C>T variant did not differ according to Fontaine or TASC categories. However, Hcy was higher in patients with the CT+TT genotypes than in those with the CC genotype (14.60 µmol/L vs. 12.94 µmol/L, p=0.008). Moreover, patients with the TT genotype had higher Hcy than those with the CC+CT genotypes (16.40 µmol/L vs. 13.22 µmol/L, p=0.019), independently of the major confounding variables.
Conclusions: The T allele of MTHFR 677C>T variant was associated with higher Hcy levels in PAD patients, but not in controls, suggesting a possible interaction between the MTHFR 677C>T variant and other genetic, epigenetic, or environmental factors associated with PAD, affecting modulation of Hcy metabolism.
期刊介绍:
The Jornal Vascular Brasileiro is editated and published quaterly to select and disseminate high-quality scientific contents concerning original research, novel surgical and diagnostic techniques, and clinical observations in the field of vascular surgery, angiology, and endovascular surgery. Its abbreviated title is J. Vasc. Bras., which should be used in bibliographies, footnotes and bibliographical references and strips.