MTHFR 677C>T (rsRS1801133) variant is associated with hyperhomocysteinemia but not with clinical severity in patients with peripheral arterial disease / A variante MTHFR 677C>T (RS1801133) está associada a hiperhomocisteinemia, mas não a gravidade clínica em pacientes com doença arterial periférica

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.

Resumo Contexto O envolvimento da variante MTHFR 677C>T na hiperhomocisteinemia e na doença arterial periférica (DAP) ainda não está claro. Objetivos Avaliar a associação da variante MTHFR 677C>T (rs1801133) com suscetibilidade e gravidade da DAP e valores séricos de homocisteína (Hcy). Métodos Este estudo caso-controle envolveu 157 pacientes com DAP e 113 controles não relacionados. A gravidade e as categorias anatomorradiológicas da DAP foram avaliadas pela classificação de Fontaine e pelo Inter-Society Consensus for the Management of Peripheral Arterial Disease, respectivamente. A genotipagem foi realizada por meio de reação em cadeia da polimerase em tempo real, e os valores de Hcy foram determinados por ensaio de micropartículas de quimioluminescência. Resultados Entre os pacientes com DAP, 97 (61,8%) eram homens e 60 (38,2%) eram mulheres, com mediana de idade de 69 anos. Os pacientes com DAP eram mais velhos e apresentaram valores mais elevados de Hcy do que os controles (mediana de 69 vs. 45 anos de idade, p < 0,001; 13,66 µmol/L vs. 9,91 µmol/L, p = 0,020, respectivamente). Os valores de Hcy foram mais elevados em pacientes com os genótipos CT+TT do que aqueles com o genótipo CC (14,60 µmol/L vs. 12,94 µmol/L, p = 0,008). Além disso, os pacientes com o genótipo TT apresentaram valores mais elevados de Hcy do que aqueles com os genótipos CC+CT (16,40 µmol/L vs. 13,22 µmol/L, p = 0,019, respectivamente), independentemente das principais variáveis confundidoras. Conclusões O alelo T da variante MTHFR 677C>T foi associado a valores mais elevados de Hcy nos pacientes com DAP, mas não em controles, sugerindo uma possível interação entre a variante genética MTHFR 677C>T e outros fatores genéticos, epigenéticos ou ambientais associados com a DAP na modulação do metabolismo da Hcy.

The Characteristics and Factors Affecting Patients Diagnosed with Lower Limb Arteriosclerosis Obliterans in an Emergency Department

PURPOSE: This study investigated the relationship between the laboratory results of patients diagnosed with lower limb arteriosclerosis obliterans (LASO) in an emergency department (ED), general characteristics, clinical manifestation, hematological conditions, and clinical views of severity. Another purpose of the study was to determine the factors that could contribute to clinical severity to facilitate the prediction and diagnosis of LASO in the ED. METHODS: From January 2005 to December 2012 we conducted a retrospective study on patients diagnosed with LASO in the ED. Included in the study were 52 patients diagnosed with LASO through CT. The patients were divided into two groups according to the Fontaine classification-for comparative analysis: "less severe" (for stage II and below) and "more severe" (for stage III and above). Vital signs, clinical findings, laboratory data, and CT findings were analyzed in each patient. The SPSS package with the Mann-Whitney U test, Fisher's exact test, and logistic regression were used for data analysis. A p-value <0.05 was considered statistically significant. RESULTS: The average age of patients diagnosed with LASO was 73.1+/-10.1 and male saccounted for 76.9% of the population (n=40). Based upon the levels of severity by the Fontaine classification, patients were divided into 28 "more severe" and 24 "less severe" cases. The "more severe" LASO patients showed a high pulse rate (p=0.017) and a higher current smoking rate (p=0.04). The laboratory data from "more severe" LASO patients showed significant differences in total white blood cell count (p=0.040), erythrocyte sedimentation rate (p=0.000), and the levels of lactate dehydrogenase (p=0.002), creatine kinase (p=0.000), creatine kinase-MB (p=0.002), myoglobin (p=0.000), and C-reactive protein (p=0.000). The significant factors that could affect clinical severity were erythrocyte sedimentation rate (OR 1.066, 95% CI 1.010-1.125, p=0.021), and the levels of lactate dehydrogenase (OR 1.015, 95% CI 1.002-1.029, p=0.027), creatine kinase-MB (OR 1.229, 95% CI 1.028-1.468, p=0.023), and C-reactive protein (OR 1.533, 95% CI 1.074-2.188, p=0.019). CONCLUSION: The patients diagnosed with more severe LASO showed a high pulse rate, a higher current smoking rate, high levels of inflammation (erythrocyte sedimentation rate and C-reactive protein), and high levels of muscle enzymes (lactate dehydrogenase, creatine kinase, myogolobin, creatine kinase-MB). The factors that could influence clinical severity were erythrocyte sedimentation rate, and the levels of lactate dehydrogenase, creatine kinase-MB, and C-reactive protein.

The Characteristics and Factors Affecting Patients Diagnosed with Lower Limb Arteriosclerosis Obliterans in an Emergency Department

PURPOSE: This study investigated the relationship between the laboratory results of patients diagnosed with lower limb arteriosclerosis obliterans (LASO) in an emergency department (ED), general characteristics, clinical manifestation, hematological conditions, and clinical views of severity. Another purpose of the study was to determine the factors that could contribute to clinical severity to facilitate the prediction and diagnosis of LASO in the ED. METHODS: From January 2005 to December 2012 we conducted a retrospective study on patients diagnosed with LASO in the ED. Included in the study were 52 patients diagnosed with LASO through CT. The patients were divided into two groups according to the Fontaine classification-for comparative analysis: "less severe" (for stage II and below) and "more severe" (for stage III and above). Vital signs, clinical findings, laboratory data, and CT findings were analyzed in each patient. The SPSS package with the Mann-Whitney U test, Fisher's exact test, and logistic regression were used for data analysis. A p-value <0.05 was considered statistically significant. RESULTS: The average age of patients diagnosed with LASO was 73.1+/-10.1 and male saccounted for 76.9% of the population (n=40). Based upon the levels of severity by the Fontaine classification, patients were divided into 28 "more severe" and 24 "less severe" cases. The "more severe" LASO patients showed a high pulse rate (p=0.017) and a higher current smoking rate (p=0.04). The laboratory data from "more severe" LASO patients showed significant differences in total white blood cell count (p=0.040), erythrocyte sedimentation rate (p=0.000), and the levels of lactate dehydrogenase (p=0.002), creatine kinase (p=0.000), creatine kinase-MB (p=0.002), myoglobin (p=0.000), and C-reactive protein (p=0.000). The significant factors that could affect clinical severity were erythrocyte sedimentation rate (OR 1.066, 95% CI 1.010-1.125, p=0.021), and the levels of lactate dehydrogenase (OR 1.015, 95% CI 1.002-1.029, p=0.027), creatine kinase-MB (OR 1.229, 95% CI 1.028-1.468, p=0.023), and C-reactive protein (OR 1.533, 95% CI 1.074-2.188, p=0.019). CONCLUSION: The patients diagnosed with more severe LASO showed a high pulse rate, a higher current smoking rate, high levels of inflammation (erythrocyte sedimentation rate and C-reactive protein), and high levels of muscle enzymes (lactate dehydrogenase, creatine kinase, myogolobin, creatine kinase-MB). The factors that could influence clinical severity were erythrocyte sedimentation rate, and the levels of lactate dehydrogenase, creatine kinase-MB, and C-reactive protein.