[Effect of polymorphisms on key enzymes in homocysteine metabolism, on plasma homocysteine level and on coronary artery-disease risk in a Tunisian population].
BACKGROUND
Hyperhomocysteinemia is known as an independent-risk factor for coronary-artery disease (CAD). However, the effect of homocystein metabolic enzymes polymorphisms on CAD is still controversed. We investigated the relation between homocystein metabolic key enzymes polymorphisms, homocystenemia and coronary stenosis in a Tunisian population.


METHODS
Samples were collected from 251 CAD patients documented by angiography. Genotyping were performed for C677T methylene-tetrahydrofolate reductase (MTHFR), A2756G methionine-synthase (MS) and 844ins 68 cystathionine-beta-synthase (CBS). We measured fasting plasma tHcy, folate and vitamin B12.


RESULTS
There was significant increase in homocysteinemia for homozygous genotypes of C677T MTHFR (p<0.001) and A2756G MS (p=0.01), but not for 844ins68 CBS (p=0.105). Potential confounders adjusted odds-ratios for significant coronary stenosis, associated with MTHFR TT, MS GG and CBS insertion, were respectively 1.78 (p=0.041); 2.33 (p=0.036) and 0.87 (p=0.823). The effect of mutated MTHFR genotype was more pronounced on homocysteinemia (21.4+/-9.1 micromol/L; p<0.001) and coronary stenosis (OR=2.73; p=0.033) at low folatemia (< or =6.1 ng/mL).


CONCLUSIONS
MTHFR TT and MS GG genotypes increase tHcy concentration and coronary stenosis risk, especially with low folatemia.
Belkahla
R
R
UR MSP 04/28, service de biochimie, hôpital universitaire Sahloul, route Ceinture, cité Sahloul, 4054 Sousse, Tunisie.
Omezzine
A
A
Kchok
K
K
Rebhi
L
L
Ben Hadj Mbarek
I
I
Rejeb
J
J
Ben Rejeb
N
N
Slimane
N
N
Nabli
N
N
Ben Abdelaziz
A
A
Boughzala
E
E
Bouslama
A
A
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D023921:Coronary Stenosis / Q000235:genetics*; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014416:Tunisia
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003541:Cystathionine beta-Synthase