Cardiovascular diseases with multifactorial origin, resulting from the interplay of genetic and environmental factors, present a particular challenge to different medical disciplines and are frequently associated with acquired hypercholesterolaemia. So far no studies have been carried out investigating the genetic status of the cardiovascular diseases among the Hungarian population. In different populations of the world more than 150 genetic alterations of the LDL receptor gene have been identified: each of those can result in hypercholesterolaemia, but no hot spots in the gene were detected so far. Because of the very variable genetic alterations of the LDL receptor gene in different populations none of the assays developed for the detection of different mutations/deletions in the regions of the gene can be adapted to study the possible DNA damages. We have developed a new molecular biological assay which allows to screen genetic abnormalities in the whole gene in most routine laboratories. Results of numerous studies regarding the relationship between apoE polymorphism and serum lipid parameters support the hypothesis that the presence of apoE ε2 allele has protective, while that of ε4 allele has permissive effect on the development of hypercholesterolaemia and, consequently, atherosclerosis. The aims of our apoE polymorphism studies were 1) to clarify whether the accumulation of the permissive allele can be observed in hypercholesterolaemic groups; and 2) to introduce a new method based on melting point analysis in our laboratory for rapid genotyping, which offers a powerful tool for accurate and reliable mutation detection in the gene. Our newly developed rapid, effective screening test enables the simultaneous analysis of DNA alterations affecting more than 20bp in any part of the LDL receptor gene. In a relatively simple multiplex PCR system all the 18 exons and the promoter region of the gene can be amplified and analysed in 7 different reaction mixtures using primer pairs flanking completely the coding region of the gene. Analysis of 20 consecutive Hungarian hypercholesterolaemic patients was proven no large deletions or other rearrangements in the LDL receptor gene in Eastern-Hungary. 247 hypercholesterolaemic patients were involved in the apoE polymorphism study. No significant differences were found either in allele frequency or in isotype frequency distributions comparing to the reference population based on 202 healthy Hungarian blood donors. These results do not support the hypothesis that individuals homozygous or heterozygous for the ε4 allele of apoE gene have increased risk of hypercholesterolaemia, and on the basis of these findings it cannot be excluded that the high prevalence of coronary heart disease in the Eastern-Hungarian population is strongly independent of the metabolic events in which apoE isoforms participate. Today, when more and more laboratories are planning to introduce polymorphism studies as a diagnostic test for increased risk of atherosclerosis, it is important to emphasise that further studies on the interrelationships between genetic polymorphisms of different genes involved in the lipid metabolism and different forms of hypercholesterolaemia are indicated.