Diseases associated with the low copy number of the C4B gene encoding C4, the fourth component of complement

In this review article, earlier and recent work of the research group on the copy number polymorphism of the C4B gene are summarized. In a study performed in 1991 a sharp decrease was found among healthy elderly (> 60 years old) people as compared to healthy young (< 45 years old) people in the frequency of the individuals with a low copy number of the C4B gene (one of the two genes (C4A and C4B) encoding the C4 complement protein). This observation indicated that subjects with a low C4B copy number are selected out from the population of healthy individuals due to their increased morbidity/mortality of some disease(s). In accordance with this assumption a marked accumulation of low C4B copy number carriers was found in patients with acute myocardial infarction (AMI) and stroke as compared to age-matched healthy subjects. In addition it was demonstrated that AMI patients who carry a low copy number of the C4B gene have a highly significantly increased risk for short-term (1 year) post-AMI mortality as compared to non-carriers. These relationships, which were first revealed more than 15 years ago by our group, have been recently supported by new data obtained using up-to-date genotyping methods worked out by our group in two Caucasian populations, Hungarian and Icelandic. In addition, we proved that this relationship concerns only recent smokers. These findings indicate that there is strong connection between low copy number of the C4B gene on one hand and cardiovascular disease morbidity and mortality on the other. Hypotheses and the results of recent studies aiming to elucidate the mechanism of this association as well as other diseases connected with the low C4B copy number are discussed. Copyright (C) 2009 S. Karger AG, Basel