Document Detail

Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease.
MedLine Citation:
PMID:  1998339     Owner:  NLM     Status:  MEDLINE    
Severe methylenetetrahydrofolate reductase (MTHFR) deficiency with less than 2% of normal enzyme activity is characterized by neurological abnormalities, atherosclerotic changes, and thromboembolism. We have discovered a "new" variant of MTHFR deficiency which is characterized by the absence of neurological abnormalities, an enzyme activity of about 50% of the normal value, and distinctive thermolability under specific conditions of heat inactivation. In this study, lymphocyte MTHFR specific activities in the thermolabile variant and control groups were 5.58 +/- 0.91 and 10.33 +/- 2.89 nmol formaldehyde formed/mg protein/h, respectively. The difference was significant (P less than .01). However, there was overlap among the individual values from the two groups. On the other hand, residual MTHFR activity after heat inactivation was 11.2 +/- 1.43% in the thermolabile variant and 36.3 +/- 5.18% in the controls. There was no overlap. Enzyme studies in 10 subjects with thermolabile MTHFR and their family members support the hypothesis that thermolabile MTHFR is inherited as an autosomal recessive trait. To elucidate the association of thermolabile MTHFR with the development of coronary artery disease, we determined the thermostability of lymphocyte MTHFR in 212 patients with proven coronary artery disease and in 202 controls without clinical evidence of atherosclerotic vascular disease. Thermolabile MTHFR was found in 36 (17.0%) cardiac patients and 10 (5.0%) controls. The difference in incidence between the two groups was statistically significant (P less than .01). The average age at onset of clinical coronary artery disease in 36 patients with thermolabile MTHFR was 57.3 +/- 7.6 years (35-72 years). The mean total plasma homocysteine concentration in patients with thermolabile MTHFR was 13.19 +/- 5.32 nmol/ml and was significantly different from the normal mean of 8.50 +/- 2.80 nmol/ml (P less than .05). There was no association between thermolabile MTHFR and other major risk factors. We conclude that thermolabile MTHFR is a variant(s) of MTHFR deficiency which is inherited as an autosomal recessive trait. In addition, it is positively associated with the development of coronary artery disease. Determination of in vitro thermostability of lymphocyte MTHFR is a reliable method for identifying subjects with this abnormality.
S S Kang; P W Wong; A Susmano; J Sora; M Norusis; N Ruggie
Related Documents :
10477539 - Relation of atrial refractoriness to upper and lower limits of vulnerability for atrial...
20727789 - Newly diagnosed atrial fibrillation after acute ischemic stroke and transient ischemic ...
11846859 - Assessment of new onset postcoronary artery bypass surgery atrial fibrillation: current...
10711089 - Atrial fibrillation in the older adult. presentation and management issues.
17631079 - Comparison of rate versus rhythm control for atrial fibrillation in patients with left ...
15474699 - Impairment of left atrial function predicts post-operative atrial fibrillation after co...
16164199 - Abnormal sympathetic innervation of the heart in a patient with emery-dreifuss muscular...
8076069 - Surgical treatment of cardiac myxoma and its complications.
19122579 - Optimizing outcomes in coronary ct imaging.
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of human genetics     Volume:  48     ISSN:  0002-9297     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  1991 Mar 
Date Detail:
Created Date:  1991-04-03     Completed Date:  1991-04-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  536-45     Citation Subset:  IM    
Department of Pediatrics, Rush Medical College, Chicago, IL 60612.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Aged, 80 and over
Coronary Disease / enzymology,  genetics*
Enzyme Activation
Gene Frequency
Genes, Recessive
Genetic Variation*
Heterozygote Detection
Homocysteine / blood*
Hot Temperature
Lymphocytes / enzymology
Methylenetetrahydrofolate Reductase (NADPH2)
Middle Aged
Oxidoreductases Acting on CH-NH Group Donors / deficiency*,  genetics
Risk Factors
Grant Support
Reg. No./Substance:
454-28-4/Homocysteine; EC 1.5.-/Oxidoreductases Acting on CH-NH Group Donors; EC Reductase (NADPH2)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Cloning and expression of the cDNA encoding human fumarylacetoacetate hydrolase, the enzyme deficien...
Next Document:  Intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolat...