Document Detail


Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease.
MedLine Citation:
PMID:  1998339     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S S Kang; P W Wong; A Susmano; J Sora; M Norusis; N Ruggie
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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    
Affiliation:
Department of Pediatrics, Rush Medical College, Chicago, IL 60612.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Child
Coronary Disease / enzymology,  genetics*
Enzyme Activation
Female
Gene Frequency
Genes, Recessive
Genetic Variation*
Heterozygote Detection
Homocysteine / blood*
Hot Temperature
Humans
Lymphocytes / enzymology
Male
Methylenetetrahydrofolate Reductase (NADPH2)
Middle Aged
Oxidoreductases Acting on CH-NH Group Donors / deficiency*,  genetics
Risk Factors
Grant Support
ID/Acronym/Agency:
HL 36135/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
454-28-4/Homocysteine; EC 1.5.-/Oxidoreductases Acting on CH-NH Group Donors; EC 1.5.1.20/Methylenetetrahydrofolate Reductase (NADPH2)
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