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Contains fulltext : 53106.pdf (publisher's version ) (Closed access), BACKGROUND: Hyperhomocysteinemia has been associated with vascular disease in many epidemiologic studies, but only a few have reported on the relation between hyperhomocysteinemia and aneurysms of the abdominal aorta (AAAs). Although these studies showed higher homocysteine concentrations in patients with AAA than in controls, little attention had been given to possible confounding factors. Most patients with AAA are of older age, have an impaired renal function, and have other risk factors for cardiovascular disease. This matched case-control study investigated the relation between homocysteine concentration (before and after methionine loading) and AAA, taking into account possible confounders such as age, sex, and concentrations of creatinine and B vitamins. METHODS: Patients with a history of AAA were recruited from the outpatient clinic; 60% had already undergone surgery for their AAA. They were asked to invite a friend or neighbor to participate as a control subject (age-matched and sex-matched). Concentrations of homocysteine, vitamin B6, vitamin B12, folate, and creatinine were determined in the fasting state, and blood was taken for methylenetetrahydrofolate reductase (MTHFR) mutation analysis. Six hours after oral methionine loading, the postmethionine load homocysteine concentration was determined. RESULTS: Univariate analysis showed an odds ratio (OR) of 2.2 (95% confidence interval (CI), 0.9 to 5.5) for the risk of AAA for the highest quartile of homocysteine concentration. After adjustment for creatinine, the OR was markedly reduced to 1.24 (95% CI, 0.42 to 3.66), and this risk further attenuated in the multivariate analysis. Univariate analysis of the B vitamins showed an increased risk of AAA for the bottom quartile of vitamin B6 (OR, 3.75; 95% CI, 1.22 to 11.54), which even increased after adjustments. The relative risk associated with the MTHFR 677TT polymorphism was 2.1 (95% CI, 0.9 to 5.3). CONCLUSION: Vitamin B6, but not homocysteine, is an inde

Contains fulltext : 53106.pdf (publisher's version ) (Closed access), BACKGROUND: Hyperhomocysteinemia has been associated with vascular disease in many epidemiologic studies, but only a few have reported on the relation between hyperhomocysteinemia and aneurysms of the abdominal aorta (AAAs). Although these studies showed higher homocysteine concentrations in patients with AAA than in controls, little attention had been given to possible confounding factors. Most patients with AAA are of older age, have an impaired renal function, and have other risk factors for cardiovascular disease. This matched case-control study investigated the relation between homocysteine concentration (before and after methionine loading) and AAA, taking into account possible confounders such as age, sex, and concentrations of creatinine and B vitamins. METHODS: Patients with a history of AAA were recruited from the outpatient clinic; 60% had already undergone surgery for their AAA. They were asked to invite a friend or neighbor to participate as a control subject (age-matched and sex-matched). Concentrations of homocysteine, vitamin B6, vitamin B12, folate, and creatinine were determined in the fasting state, and blood was taken for methylenetetrahydrofolate reductase (MTHFR) mutation analysis. Six hours after oral methionine loading, the postmethionine load homocysteine concentration was determined. RESULTS: Univariate analysis showed an odds ratio (OR) of 2.2 (95% confidence interval (CI), 0.9 to 5.5) for the risk of AAA for the highest quartile of homocysteine concentration. After adjustment for creatinine, the OR was markedly reduced to 1.24 (95% CI, 0.42 to 3.66), and this risk further attenuated in the multivariate analysis. Univariate analysis of the B vitamins showed an increased risk of AAA for the bottom quartile of vitamin B6 (OR, 3.75; 95% CI, 1.22 to 11.54), which even increased after adjustments. The relative risk associated with the MTHFR 677TT polymorphism was 2.1 (95% CI, 0.9 to 5.3). CONCLUSION: Vitamin B6, but not homocysteine, is an inde

Contains fulltext : 53106.pdf (publisher's version ) (Closed access), BACKGROUND: Hyperhomocysteinemia has been associated with vascular disease in many epidemiologic studies, but only a few have reported on the relation between hyperhomocysteinemia and aneurysms of the abdominal aorta (AAAs). Although these studies showed higher homocysteine concentrations in patients with AAA than in controls, little attention had been given to possible confounding factors. Most patients with AAA are of older age, have an impaired renal function, and have other risk factors for cardiovascular disease. This matched case-control study investigated the relation between homocysteine concentration (before and after methionine loading) and AAA, taking into account possible confounders such as age, sex, and concentrations of creatinine and B vitamins. METHODS: Patients with a history of AAA were recruited from the outpatient clinic; 60% had already undergone surgery for their AAA. They were asked to invite a friend or neighbor to participate as a control subject (age-matched and sex-matched). Concentrations of homocysteine, vitamin B6, vitamin B12, folate, and creatinine were determined in the fasting state, and blood was taken for methylenetetrahydrofolate reductase (MTHFR) mutation analysis. Six hours after oral methionine loading, the postmethionine load homocysteine concentration was determined. RESULTS: Univariate analysis showed an odds ratio (OR) of 2.2 (95% confidence interval (CI), 0.9 to 5.5) for the risk of AAA for the highest quartile of homocysteine concentration. After adjustment for creatinine, the OR was markedly reduced to 1.24 (95% CI, 0.42 to 3.66), and this risk further attenuated in the multivariate analysis. Univariate analysis of the B vitamins showed an increased risk of AAA for the bottom quartile of vitamin B6 (OR, 3.75; 95% CI, 1.22 to 11.54), which even increased after adjustments. The relative risk associated with the MTHFR 677TT polymorphism was 2.1 (95% CI, 0.9 to 5.3). CONCLUSION: Vitamin B6, but not homocysteine, is an inde

Contains fulltext : 47727.pdf (publisher's version ) (Closed access), Elevated levels of homocysteine are a risk factor for vascular disease, thrombosis, neural tube defects and dementia. The 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene appears to be the most important single determinant of plasma homocysteine concentration. In the current study, we estimated heritability and fit a series of models of inheritance for both fasting and postmethionine-load homocysteine levels in the HOFAM-study (HOmocysteine in FAMilies study), which included 306 participants from 51 pedigrees, ascertained through a hyperhomocysteinemic proband. The crude heritability was 21.6% for fasting and 67.5% for postloading homocysteine. After adjustment for MTHFR 677C>T genotype, heritability dropped to 5.2 and 63.9%, respectively. Segregation analysis revealed that a nongenetic model with equal transmission was the best fitting and most parsimonious model for fasting homocysteine levels, while a two-distribution, Mendelian model with residual familial correlation was best for postmethionine-load homocysteine levels. This study shows that postload homocysteine levels have a stronger genetic determination than do fasting homocysteine levels. The heritability of postload homocysteine levels were not strongly affected by adjustment for MTHFR 677C>T genotype, in contrast to fasting homocysteine levels. Further studies are needed to identify the genes responsible for the inheritance of postload homocysteine levels.

Contains fulltext : 47727.pdf (publisher's version ) (Closed access), Elevated levels of homocysteine are a risk factor for vascular disease, thrombosis, neural tube defects and dementia. The 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene appears to be the most important single determinant of plasma homocysteine concentration. In the current study, we estimated heritability and fit a series of models of inheritance for both fasting and postmethionine-load homocysteine levels in the HOFAM-study (HOmocysteine in FAMilies study), which included 306 participants from 51 pedigrees, ascertained through a hyperhomocysteinemic proband. The crude heritability was 21.6% for fasting and 67.5% for postloading homocysteine. After adjustment for MTHFR 677C>T genotype, heritability dropped to 5.2 and 63.9%, respectively. Segregation analysis revealed that a nongenetic model with equal transmission was the best fitting and most parsimonious model for fasting homocysteine levels, while a two-distribution, Mendelian model with residual familial correlation was best for postmethionine-load homocysteine levels. This study shows that postload homocysteine levels have a stronger genetic determination than do fasting homocysteine levels. The heritability of postload homocysteine levels were not strongly affected by adjustment for MTHFR 677C>T genotype, in contrast to fasting homocysteine levels. Further studies are needed to identify the genes responsible for the inheritance of postload homocysteine levels.

Contains fulltext : 47727.pdf (publisher's version ) (Closed access), Elevated levels of homocysteine are a risk factor for vascular disease, thrombosis, neural tube defects and dementia. The 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene appears to be the most important single determinant of plasma homocysteine concentration. In the current study, we estimated heritability and fit a series of models of inheritance for both fasting and postmethionine-load homocysteine levels in the HOFAM-study (HOmocysteine in FAMilies study), which included 306 participants from 51 pedigrees, ascertained through a hyperhomocysteinemic proband. The crude heritability was 21.6% for fasting and 67.5% for postloading homocysteine. After adjustment for MTHFR 677C>T genotype, heritability dropped to 5.2 and 63.9%, respectively. Segregation analysis revealed that a nongenetic model with equal transmission was the best fitting and most parsimonious model for fasting homocysteine levels, while a two-distribution, Mendelian model with residual familial correlation was best for postmethionine-load homocysteine levels. This study shows that postload homocysteine levels have a stronger genetic determination than do fasting homocysteine levels. The heritability of postload homocysteine levels were not strongly affected by adjustment for MTHFR 677C>T genotype, in contrast to fasting homocysteine levels. Further studies are needed to identify the genes responsible for the inheritance of postload homocysteine levels.

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Contains fulltext : 23204___.PDF (publisher's version ) (Open Access)

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Contains fulltext : 23204___.PDF (publisher's version ) (Open Access)

Item does not contain fulltext

Contains fulltext : 23204___.PDF (publisher's version ) (Open Access)