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Methylenetetrahydrofolate reductase gene C677T polymorphism, homocysteine, vitamin B12, and DNA damage in coronary artery disease.
Hum Genet 2003; 112(2):171-7HG

Abstract

Elevated levels of plasma homocysteine (Hcy), a risk factor for coronary artery disease (CAD), can result from genetic errors, e.g., the methylenetetrahydrofolate reductase (MTHFR) polymorphism, or nutritional deficiencies, e.g., in vitamin B12 and folate. The mechanism by which Hcy induces atherosclerosis is not fully understood. Recently, Hcy has also been observed to induce DNA damage. In this study, we have investigated whether DNA damage is related to the C677T variant in the MTHFR gene and to plasma levels of Hcy, B12, and folate in patients with CAD. Patients (n=46) with angiographically proven CAD were studied by using the micronucleus (MN) test, an accepted method for evaluating genetic instability. TT patients had plasma Hcy levels higher than those with the CT or CC genotypes (27.8+/-5.2 vs 13.7+/-2.2 and 12.9+/-1.9 micro mol/l, respectively; P=0.02). Patients with multi-vessel disease had higher plasma Hcy levels (11.6+/-1.2, 22.0+/-4.7, 19.3+/-3.9 micromol/l for one-, two- and three-vessel disease, respectively; P=0.05). The MN index increased with the number of affected vessels (8.4+/-0.7, 11.1+/-2.0, 14.2+/-1.7 for one-, two-, and three-vessels disease, respectively; P=0.02) and was significantly higher in subjects with the TT genotype compared with the CC or CT genotypes (15.7+/-2.4 vs 8.9+/-1.7 and 9.9+/-0.8; P=0.02). The MN index was also correlated negatively with plasma B12 concentration (r=-0.343; P=0.019) and positively with plasma Hcy (r=0.429, P=0.005). These data indicate that the MN index is associated with the severity of CAD and is related to the MTHFR polymorphism, suggesting an interesting link between coronary atherosclerosis and genetic instability in humans.

Authors+Show Affiliations

Laboratory of Cellular Biology, CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia Sud-Montepepe, 54100 Massa, Italy. andreas@ifc.pi.cnr.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12522558

Citation

Andreassi, Maria Grazia, et al. "Methylenetetrahydrofolate Reductase Gene C677T Polymorphism, Homocysteine, Vitamin B12, and DNA Damage in Coronary Artery Disease." Human Genetics, vol. 112, no. 2, 2003, pp. 171-7.
Andreassi MG, Botto N, Cocci F, et al. Methylenetetrahydrofolate reductase gene C677T polymorphism, homocysteine, vitamin B12, and DNA damage in coronary artery disease. Hum Genet. 2003;112(2):171-7.
Andreassi, M. G., Botto, N., Cocci, F., Battaglia, D., Antonioli, E., Masetti, S., ... Clerico, A. (2003). Methylenetetrahydrofolate reductase gene C677T polymorphism, homocysteine, vitamin B12, and DNA damage in coronary artery disease. Human Genetics, 112(2), pp. 171-7.
Andreassi MG, et al. Methylenetetrahydrofolate Reductase Gene C677T Polymorphism, Homocysteine, Vitamin B12, and DNA Damage in Coronary Artery Disease. Hum Genet. 2003;112(2):171-7. PubMed PMID: 12522558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylenetetrahydrofolate reductase gene C677T polymorphism, homocysteine, vitamin B12, and DNA damage in coronary artery disease. AU - Andreassi,Maria Grazia, AU - Botto,Nicoletta, AU - Cocci,Franca, AU - Battaglia,Debora, AU - Antonioli,Elisabetta, AU - Masetti,Serena, AU - Manfredi,Samantha, AU - Colombo,Maria Giovanna, AU - Biagini,Andrea, AU - Clerico,Aldo, Y1 - 2002/11/13/ PY - 2002/06/12/received PY - 2002/09/10/accepted PY - 2003/1/11/pubmed PY - 2003/2/27/medline PY - 2003/1/11/entrez SP - 171 EP - 7 JF - Human genetics JO - Hum. Genet. VL - 112 IS - 2 N2 - Elevated levels of plasma homocysteine (Hcy), a risk factor for coronary artery disease (CAD), can result from genetic errors, e.g., the methylenetetrahydrofolate reductase (MTHFR) polymorphism, or nutritional deficiencies, e.g., in vitamin B12 and folate. The mechanism by which Hcy induces atherosclerosis is not fully understood. Recently, Hcy has also been observed to induce DNA damage. In this study, we have investigated whether DNA damage is related to the C677T variant in the MTHFR gene and to plasma levels of Hcy, B12, and folate in patients with CAD. Patients (n=46) with angiographically proven CAD were studied by using the micronucleus (MN) test, an accepted method for evaluating genetic instability. TT patients had plasma Hcy levels higher than those with the CT or CC genotypes (27.8+/-5.2 vs 13.7+/-2.2 and 12.9+/-1.9 micro mol/l, respectively; P=0.02). Patients with multi-vessel disease had higher plasma Hcy levels (11.6+/-1.2, 22.0+/-4.7, 19.3+/-3.9 micromol/l for one-, two- and three-vessel disease, respectively; P=0.05). The MN index increased with the number of affected vessels (8.4+/-0.7, 11.1+/-2.0, 14.2+/-1.7 for one-, two-, and three-vessels disease, respectively; P=0.02) and was significantly higher in subjects with the TT genotype compared with the CC or CT genotypes (15.7+/-2.4 vs 8.9+/-1.7 and 9.9+/-0.8; P=0.02). The MN index was also correlated negatively with plasma B12 concentration (r=-0.343; P=0.019) and positively with plasma Hcy (r=0.429, P=0.005). These data indicate that the MN index is associated with the severity of CAD and is related to the MTHFR polymorphism, suggesting an interesting link between coronary atherosclerosis and genetic instability in humans. SN - 0340-6717 UR - https://www.unboundmedicine.com/medline/citation/12522558/Methylenetetrahydrofolate_reductase_gene_C677T_polymorphism_homocysteine_vitamin_B12_and_DNA_damage_in_coronary_artery_disease_ L2 - https://dx.doi.org/10.1007/s00439-002-0859-3 DB - PRIME DP - Unbound Medicine ER -