Intermediate and Severe Hyperhomocysteinemia with Thrombosis: A Study of Genetic Determinants

Autor: Niels Rüdiger, Karsten Rasmussen, Mette Gaustadnes, Jørgen Ingerslev
Rok vydání: 2000
Předmět:
Adult
Male
congenital
hereditary
and neonatal diseases and abnormalities
medicine.medical_specialty
Hyperhomocysteinemia
Pathology
Genotype
Homocysteine
Denmark
DNA Mutational Analysis
Cystathionine beta-Synthase
Compound heterozygosity
Severity of Illness Index
Gastroenterology
Cohort Studies
Genetic Heterogeneity
chemistry.chemical_compound
Gene Frequency
Risk Factors
Thromboembolism
Internal medicine
medicine
Humans
Point Mutation
Thrombophilia
Genetic Predisposition to Disease
Age of Onset
Allele frequency
Methylenetetrahydrofolate Reductase (NADPH2)
Oxidoreductases Acting on CH-NH Group Donors
biology
business.industry
Genetic heterogeneity
nutritional and metabolic diseases
Thrombosis
Hematology
Middle Aged
medicine.disease
Cystathionine beta synthase
Stroke
Phenotype
Amino Acid Substitution
chemistry
Methylenetetrahydrofolate reductase
biology.protein
Female
business
Zdroj: Thrombosis and Haemostasis. 83:554-558
ISSN: 2567-689X
0340-6245
DOI: 10.1055/s-0037-1613862
Popis: SummaryHyperhomocysteinemia is an independent risk factor for cardiovascular disease. In search of genetic factors causing elevated levels of total homocysteine in plasma (tHcy), we investigated a cohort of consecutively identified, unrelated thrombosis patients (n = 28) having intermediate or severe hyperhomocysteinemia (30 µmol/l100 µmol/l, respectively). The methylenetetrahydrofolate reductase (MTHFR) 677C→T genotype, and the complete cystathionine β-synthase (CBS) genotype was determined in all patients. We found that the MTHFR T/T genotype was strongly correlated with intermediate hyperhomocysteinemia, being present in 73.9 % of those cases (17 of 23). In three of five patients with severe hyperhomocysteinemia, compound heterozygosity for CBS mutations was detected. Among the mutations, two novel missense mutations: 1265C→T (S422L) and 1397C→T (S466L) were detected. The phenotype in those patients was quite mild, thromboembolism apart. This indicates that a search for CBS mutations in patients with severe hyperhomocysteinemia is important to ensure the detection of a possible CBS deficiency, thus enabling treatment. Co-existence of the MTHFR T/T genotype and the common CBS 844ins68 variant was significantly higher among patients (10.7%) as compared to controls (1.2%), indicating that this genotype combination is a thrombotic risk factor (P Abbreviations: MTHFR, methylenetetrahydrofolate reductase; CBS, cystathionine β-synthase; tHcy, total homocysteine in plasma.
Databáze: OpenAIRE
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