Genome-wide association reveals that common genetic variation in the kallikrein-kinin system is associated with serum L-arginine levels.

L-arginine is the essential precursor of nitric oxide, and is involved in multiple key physiological processes, including vascular and immune function. The genetic regulation of blood L-arginine levels is largely unknown. We performed a genome-wide association study (GWAS) to identify genetic factors determining serum L-arginine levels, amongst 901 Europeans and 1,394 Indian Asians.

The causal roles of vitamin B(12) and transcobalamin in prostate cancer: can Mendelian randomization analysis provide definitive answers?

Circulating vitamin B(12) (cobalamin/B(12)) and total transcobalamin (tTC) have been associated with increased and reduced risk, respectively, of prostate cancer. Mendelian randomization has the potential to determine whether these are causal associations. We estimated associations of single nucleotide polymorphisms in B(12)-related genes (MTR, MTRR, FUT2, TCN2, TCN1, CUBN, and MUT) with plasma concentrations of B(12), tTC, holo-transcobalamin, holo-haptocorrin, folate, and homocysteine and with prostate cancer risk in a case-control study (913 cases, 895 controls) nested within the UK-wide population-based ProtecT study of prostate cancer in men age 45-69 years.

Folate and cobalamin status in relation to diet in healthy 2-y-old children.

Background: Limited data exist on sources of folate and cobalamin in the toddler diet.

Objective: We examined the influence of diet on folate and cobalamin status in healthy toddlers in an unfortified population.

Design: Dietary intake was assessed in 178 children, aged 24 mo, by using 7-d food records and related to serum folate and cobalamin status in 155 children.

Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer.

Background: Vitamin B(12), holo-haptocorrin, and the folate-pathway single-nucleotide polymorphisms MTR 2756A>G and SHMT1 1420C>T have been associated with an increased risk of prostate cancer. We investigated whether these and other elements of folate metabolism were associated with prostate-specific antigen (PSA) velocity (PSAV) as a proxy measure of prostate cancer progression in men with localized prostate cancer.

Methods: We measured plasma folate, B(12), holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine at diagnosis in 424 men (ages 45-70 years) with localized prostate cancer in a U.

Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial.

Background: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.

Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis.

Background: Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B(12), and related metabolites were associated with prostate cancer risk.

Methods: Matched case-control study nested within the U.

Maternal folate and cobalamin status predicts vitamin status in newborns and 6-month-old infants.

Our aim in this longitudinal study was to determine predictors of folate and cobalamin status in infancy. Data were collected from 364 mother-infant pairs with blood measurements from pregnancy ( approximately 18 wk; n = 149), newborns (cord serum; n = 361), and 6-mo-old partially or exclusively breast-fed children (n = 221). Serum/plasma folate, cobalamin, holotranscobalamin (holoTC), holohaptocorrin (holoHC), methylmalonic acid (MMA) and total homocysteine (tHcy) at birth and 6 mo were related to maternal vitamin status, parity, lifestyle variables, and anthropometry.

Increases in plasma holotranscobalamin can be used to assess vitamin B-12 absorption in individuals with low plasma vitamin B-12.

Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations.

Genetic variation in homocysteine metabolism, cognition, and white matter lesions.

Several studies have shown an association between homocysteine concentration and cognitive performance or cerebral white matter lesions. However, variations in genes encoding for enzymes and other proteins that play a role in homocysteine metabolism have hardly been evaluated in relation to these outcome measures. In the population-based Rotterdam Scan Study, we examined the association of seven polymorphisms of genes involved in homocysteine metabolism (MTHFR 677C>T, MTHFR 1298A>C, RFC 80G>A, TC 776C>G, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68) with plasma total homocysteine, cognitive performance, and cerebral white matter lesions among 1011 non-demented elderly participants.

Folate and cobalamin status in relation to breastfeeding and weaning in healthy infants.

Background: Folate and cobalamin status changes markedly during infancy.

Objective: We aimed to examine the influence of breastfeeding on folate and cobalamin status in healthy infants.

Design: In a longitudinal study, we measured serum folate, cobalamin, holotranscobalamin, holohaptocorrin, methylmalonic acid, and homocysteine at birth and at ages 6, 12, and 24 mo (n = 361, 262, 244, and 224, respectively).

Polymorphisms in the catechol-O-methyltransferase (COMT) gene influence plasma total homocysteine levels.

Elevated plasma total homocysteine (tHcy) is a risk factor for various disorders. We investigated whether functional polymorphisms in catechol-O-methyltransferase (COMT) influence tHcy, since COMT activity produces S-adenosylhomocysteine (SAH), a homocysteine precursor. We hypothesized that high activity COMT variants would be associated with high tHcy, since they presumably result in increased formation of SAH.

Homocysteine and cognitive performance: modification by the ApoE genotype.

We hypothesized that the magnitude of the association between plasma homocysteine concentration and cognitive performance is larger for ApoE-epsilon4 carriers than for non-carriers. Nine hundred eleven dementia-free and stroke-free subjects (59% women) from the Maine-Syracuse study (26-98 years old) were stratified into no-ApoE-epsilon4 (n=667) and ApoE-epsilon4 carrier (n=244) cohorts. Employing a cross-sectional design and multiple regression analyses, plasma homocysteine was related to multiple domains of cognitive performance within these cohorts.

Plasma folate concentration and cognitive performance: Rotterdam Scan Study.

Background: Evidence is increasing for beneficial and independent effects of folate on cognitive function, but the underlying biologic mechanism is as yet unknown.

Objective: We examined the independent association of plasma folate concentration with cognitive performance and explored the nature of this association by evaluating brain-imaging markers for cerebrovascular disease and brain cell loss.

Design: In the population-based Rotterdam Scan Study, 1033 nondemented participants aged 60-90 y underwent extensive cognitive testing and brain imaging.

Homocysteine, folate, and vitamins B6 and B12 blood levels in relation to cognitive performance: the Maine-Syracuse study.

Objective: Our objective was to examine associations among plasma homocysteine concentrations (tHcy), the tHcy-cofactors (folate, vitamins B6 and B12), and multiple domains of cognitive performance, with statistical adjustment for possible confounds, including cardiovascular disease risk factors (CVD-RF) and cardiovascular disease (CVD).

Methods: Subjects were 812 participants (58% women) of the Maine-Syracuse study who were free of dementia and stroke. Employing a cross-sectional design and multiple regression analyses, fasting concentrations of tHcy and its vitamin cofactors (folate, B6, and B12) were related to multiple domains of cognitive performance.

Holotranscobalamin and total transcobalamin in human plasma: determination, determinants, and reference values in healthy adults.

Background: We developed microbiological assays (MBAs) to identify determinants and to establish reference values for cobalamin bound to transcobalamin [holotranscobalamin (holoTC)] and total TC in plasma.

Methods: We captured holoTC with magnetic beads with TC antibodies and used a conventional MBA for cobalamin measurements. Total TC was determined as holoTC after TC was saturated with cyanocobalamin.

Medial temporal lobe atrophy, apolipoprotein genotype, and plasma homocysteine in Sri Lankan patients with Alzheimer's disease.

The authors studied the association of Alzheimer's disease (AD) with total plasma homocysteine (tHcy) and apolipoprotein E (apoE) genotype, and the usefulness of measuring medial temporal lobe thickness (MTL) thickness for the diagnosis of AD in Sri Lankan patients. Using criteria of the NINCDS-ADRDA, 23 AD patients and 21 controls were recruited. All underwent MTL-oriented computed tomographic (CT) scans, measurement of plasma tHcy, and apoE genotyping.

Facts and recommendations about total homocysteine determinations: an expert opinion.

Background: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations.

Screening for vitamin B-12 and folate deficiency in older persons.

Background: Vitamin B-12 deficiency is usually accompanied by elevated concentrations of serum total homocysteine (tHcy) and methylmalonic acid (MMA). Folate deficiency also results in elevated tHcy. Measurement of these metabolites can be used to screen for functional vitamin B-12 or folate deficiency.