Gene--nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population.
BACKGROUND
Elevated plasma total homocysteine is a major risk for coronary artery disease (CAD). Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine metabolism; a common C677T mutation in the MTHFR gene results in decreased enzyme activity, and contributes to increased homocysteine levels and decreased folate levels. We investigated the frequency of MTHFR C677T alleles in a Korean population, determined the genotype-specific threshold levels of folate or vitamin B12, and investigated the relationship between the TT genotype and the risk of CAD.


METHODS
We enrolled a study population of 163 CAD patients and 50 control subjects, and screened the MTHFR C677T polymorphism using real-time PCR with melting point analysis. Levels of plasma homocysteine, folate and vitamin B12 were also determined. We then defined the genotype-specific threshold values of folate and vitamin B12 required to keep homocysteine levels in a normal range for individuals of each MTHFR C677T genotype.


RESULTS
The frequency of the TT genotype was 18% in control subjects and 26% in patients group (P>0.05). Individuals homozygous for the TT genotype had significantly elevated homocysteine levels (P<0.05). The genotype-specific folate threshold level was significantly higher in TT individuals than in the CC or CT genotypes. The OR of individuals with low folate status and the TT genotype to estimate the relative risk of CAD was 2.2 and the OR of those with high folate status and the TT genotype was 1.5 (95% CI, 0.5-9.6 and 0.7-3.2, respectively).


CONCLUSIONS
We were able to define a gene-nutrient interaction that shows a higher risk for CAD based on specific threshold folate levels required by different MTHFR C677T genotypes in a Korean population.
Huh
Hee Jin
HJ
Department of Laboratory Medicine, College of Medicine, University of Ulsan and Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, 138-736 Seoul, South Korea.
Chi
Hyun Sook
HS
Shim
Eun Hee
EH
Jang
Seongsoo
S
Park
Chan Jeoung
CJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism*; D005838:Genotype; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009752:Nutritional Status; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12