Prevalence of familial mild hyperhomocysteinemia

Franken, D. G.; Boers, G.H.J.; Blom, Henk J.; Cruysberg, J.R.M.; Trijbels, Frans J.M.; Hamel, B.C.J.

doi:10.1016/0021-9150(96)05849-2

Cited by 29 publications

(18 citation statements)

References 31 publications

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“…Among the vitamins, folate and cobalamin in serum/ plasma show the strongest association with tHcy. The relation between vitamin B 6 and tHcy is weaker (23,24), and optimal vitamin B 6 function seems of particular importance only to control tHcy following a methionine load (25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (> or = 40 micromol/liter). The Hordaland Homocysteine Study.

Guttormsen¹,

Ueland²,

Nesthus³

et al. 1996

J. Clin. Invest.

256

127

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From 1992-93, we screened 18,043 subjects, aged 40-67 yr, and found 67 cases (0.4%) with total plasma homocysteine (tHcy) Ն 40 mol/liter. Compared to 329 controls, the cases had lower plasma folate and cobalamin levels, lower intake of vitamin supplements, consumed more coffee, and were more frequently smokers. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase gene was observed in 73.1% of the cases and 10.2% of the controls. Only seven cases with cobalamin deficiency and one with homocystinuria received specific therapeutic instructions. 2 yr after the screening, 58 subjects were reinvestigated. 41 still had tHcy Ͼ 20 mol/liter, and in 37 of these, intervention with low dose folic acid (0.2 mg/d) was started. Notably, 34 of 37 (92%) had homozygosity for the C677T mutation. Plasma tHcy was reduced in all but two after 7 wk, and became normal within 7 mo in 21 of 37 subjects.

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Section: Discussionmentioning

confidence: 99%

Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (> or = 40 micromol/liter). The Hordaland Homocysteine Study.

Guttormsen¹,

Ueland²,

Nesthus³

et al. 1996

J. Clin. Invest.

256

127

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“…50 Furthermore, post-load mild hyperhomocysteinaemia was established in at least one other family member in 71% of the families, indicating a strong genetic basis for hyperhomocysteinaemia. The conclusion that hyperhomocysteinaemia is, at least partially, genetically based is in line with previous reports.…”

Section: Hyperhomocysteinaemiamentioning

confidence: 98%

Genetics of hyperhomocysteinaemia in cardiovascular disease

2003

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Homocysteine, a sulphur amino acid, is a branch-point intermediate of methionine metabolism. It can be degraded in the transsulphuration pathway to cystathionine, or remethylated to methionine via the remethylation pathway. In both pathways, major genetic defects that cause enzyme de ciencies are associated with very high plasma homocysteine concentrations and excretion of homocystine into the urine. Mildly elevated plasma homocysteine concentrations are thought to be an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. Genetic defects in genes encoding enzymes involved in homocysteine metabolism, or depletion of important cofactors or (co)substrates for those enzymes, including folate, vitamin B 12 and vitamin B 6 , may result in elevated plasma homocysteine concentrations. Plasma homocysteine concentrations are also in uenced by dietary and lifestyle factors. In the last decade, several studies have been conducted to elucidate the genetic determinants of hyperhomocysteinaemia in patients with cardiovascular disease. We report on both environmental and genetic determinants of hyperhomocysteinaemia and give a detailed overview of all the genetic determinants that have been reported to date.

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“…Therefore, log-transformed homocysteine levels were used in all subsequent analysis. Correlation analysis and multiple linear regression models were used to assess the relationship between logtransformed homocysteine level and age, sex, vitamin B intake, body mass index, smoking, alcohol drinking, participation in sports, serum level of creatinine, folate, vitamins B 6 and B 12 . These covariates, identified as significant in the multiple regression analysis, were used to adjust homocyteine levels as possible confounders before analysis for familial correlation, heritability and segregation.…”

Section: Discussionmentioning

confidence: 99%

“…Age, serum creatinine, folate and serum vitamin B 12 level were significantly associated with the log-homocysteine level for both pre-and postloading homocysteine levels when multiple regression models were examined. Therefore, we considered age, sex, vitamin B intake history, serum levels of creatinine, folate and vitamin B 12 and other covariates including smoking, alcohol drinking as potential confounders and used them to adjust the pre-and postloading homocytine levels before estimation familial correlations and before carrying out the segregation analysis. No adjustment of homocysteine was done in Model 1.…”

Section: Multiple Regression Modelsmentioning

confidence: 99%

Homocysteine levels – before and after methionine loading – in 51 Dutch families

et al. 2005

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Elevated levels of homocysteine are a risk factor for vascular disease, thrombosis, neural tube defects and dementia. The 677C4T 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 677C4T 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 677C4T 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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Prevalence of familial mild hyperhomocysteinemia

Cited by 29 publications

References 31 publications

Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (> or = 40 micromol/liter). The Hordaland Homocysteine Study.

Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (> or = 40 micromol/liter). The Hordaland Homocysteine Study.

Genetics of hyperhomocysteinaemia in cardiovascular disease

Homocysteine levels – before and after methionine loading – in 51 Dutch families

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