title: Mutation A1298C of methylenetetrahydrofolate reductase: risk for early coronary disease not associated with hyperhomocysteinemia.
abstract: Diminished activity of 5,10 methylenetetrahydrofolate reductase (MTHFR), a regulatory enzyme of homocysteine metabolism, may predispose to coronary artery disease (CAD). In a case-control study we determined the prevalence of two common MTHFR polymorphisms, C677T and A1298C, in 161 male patients under the age of 50 years with angiographically documented CAD and compared it to that in 211 healthy controls. Genotyping was also performed in a random population sample, consisting of 149 men and 121 women at an average age of 40 years. The studied group had classic risk factors of atherosclerosis but did not differ in fasting plasma homocysteine, folic acid, and vitamin B12 levels in either the control group or population sample. The frequency of the 1298C allele was significantly higher in CAD (0.304) than in controls (0.199) or the population sample (0.235). Allele 1298C showed a significant association with early-onset CAD both in homozygotes and in heterozygous carriers. These findings were further supported by comparisons with the population sample. Homozygosity for allele 677T showed a tendency to associate with CAD. Allele 1298C of MTHFR is associated with early-onset CAD (carriers- RR = 1.71, 95% CI: 1.13-2.59; homozygotes- RR = 3.09, 95% CI: 1.36-7.02), even when blood homocysteine levels are not elevated.
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, 8 Skawinska Street, 31-066 Cracow, Poland. mmszczek@cyf-kr.edu.pl
authors.forename: A
authors.initials: A
authors.lastname: Szczeklik
authors.forename: M
authors.initials: M
authors.lastname: Sanak
authors.forename: M
authors.initials: M
authors.lastname: Jankowski
authors.forename: J
authors.initials: J
authors.lastname: Dropiński
authors.forename: R
authors.initials: R
authors.lastname: Czachór
authors.forename: J
authors.initials: J
authors.lastname: Musiał
authors.forename: I
authors.initials: I
authors.lastname: Axenti
authors.forename: M
authors.initials: M
authors.lastname: Twardowska
authors.forename: T
authors.initials: T
authors.lastname: Brzostek
authors.forename: M
authors.initials: M
authors.lastname: Tendera
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006720:Homozygote; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)