Genetics of intima-media thickness.
OBJECTIVE
Increased carotid artery intima-media thickness is associated with an increased risk of coronary heart disease or cerebrovascular disease and is a powerful predictor of cardiovascular and cerebrovascular outcomes. Consequently, the measurement is now used in a number of case control, cohort and familial and linkage studies as an intermediate phenotype for the investigation of the genetic and environmental determinants of atherosclerosis. The aim of this paper is to review the most recent available data on the genetic determinants of carotid intima-media thickness.


RESULTS
Genes could account for a significant amount of variation in carotid intima-media thickness: up to 30-66%. Carotid intima-media thickness progressed more rapidly with age in familial hypercholesterolemia patients than in patients without his condition. Familial hypercholesterolemia patients with a null LDL receptor allele tended to have higher carotid intima-media thickness than patients carrying the LDL receptor defective allele. Small association studies showing positive or negative results with the angiotensinogen gene variants as well as with the angiotensin converting enzyme I/D polymorphism add to the confusion in this largely controversial area. Differing results may depend on the vascular territory and genetic background. New associations have been described in small studies.


CONCLUSIONS
Studies on the association of polymorphisms and intima-media thickness are frequently disappointing and lead occasionally to conflicting results. Among study limitations is the fact that mostly single gene effects are considered; longitudinal cohort studies may be more appropriate than case control studies. Ongoing large prospective population studies and clinical trials have integrated the measurements of intima-media thickness and genotype determination with a genomic approach. As a result, in the near future we may see more important and robust results with significant consequences on our understanding of genetic determinants of atherosclerotic cardiovascular disease.
Zannad
Faiez
F
Department of Cardiovascular Disease, Division of Hypertension and Preventive Cardiology, Equipe d'Accueil 3447, Clinical Investigation Center INSERM-CHU, University Henri Poincaré, Nancy, France. cic@chu-nancy.fr
Benetos
Athanase
A
D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D002340:Carotid Artery Diseases / Q000235:genetics* / Q000473:pathology*; D005838:Genotype; D006801:Humans; D012307:Risk Factors; D017539:Tunica Intima / Q000033:anatomy & histology*; D017540:Tunica Media / Q000033:anatomy & histology*