The genetic basis of lipoprotein disorders. Introduction and overview

In order to elucidate the genetic abnormalities underlying lipoprotein disorders associated with susceptibility to coronary heart disease, researchers have looked for candidate genes. The studies have focused particularly on the lipoprotein transport genes. Relatively common as well as rare mutations have already been identified in several of these genes. In addition, further metabolic and genetic studies indicate that some of these loci harbour significant, but as yet undefined, genetic variation. In the next few years, it is not unreasonable to expect that all or most of the significant mutations at these loci will be catalogued. It is too early to know whether this will be sufficient to explain the genetic basis of altered lipoprotein levels, or whether new loci will need to be investigated. Additional candidate gene loci might be those coding for genes involved in intracellular cholesterol metabolism, cholesterol absorption or insulin resistance. New loci may also be revealed by the technique of reverse genetics. A more complete understanding of the genetics of susceptibility to atheroscerosis will probably also entail the identification of variants at genetic loci that control both the reaction of the blood vessel wall to atherogenic lipoproteins and the thrombosis system. Investigation of the genetic basis of susceptibility to coronary heart disease remains a worthwhile and lively field, with important implications for clinical and public health.