Genetic risk factors for MI in the Tyrolean population

Research project P 14040 Genetic risk factors for MI in the Tyrolean population Hans Georg KRAFT 11.10.1999 A family based association study shall be performed to determine whether the genetic factors apo(a) / Lp(a) are risk factors for myocardial infarction (MI) in the Austrian province of the Tyrol. Lp(a) is a complex in human plasma consisting of a LDL particle and apolipoprotein(a) (apo(a)) both linked via a disulfide bond. Lp(a) is a quantitative trait in human plasma which is determined by the action of one major gene - the structural gene for apo(a). Numerous case - control studies have shown that Lp(a) plasma levels are higher in CHD patients than in controls. Nevertheless due to the inherent problems of case control studies and also because of conflicting results from prospective studies the significance of Lp(a) and apo(a) as risk factor for CHD is still doubted by several investigators. Based on the "Koronarregister" of the Tyrol that is a database containing information on MI patients these will be contacted to participate in the study together with their parents and/or sibs, and children. At present the database contains data of more than 550 patients from which between 150 200 are expected to participate together with their parents, sibs and children. In addition, a control population sample will be collected consisting of two age and sex matched controls for every MI patient. Three study designs shall be employed. One is the transmission disequilibrium. test (TDT) that is based on the analysis of nuclear families (parents and an affected child) and its newest version the RC-TDT that makes also use of families that are not complete but can be reconstructed. The latter is of special interest for MI that is a late onset disease in which the probability that both parents of a diseased subject are alive is rather small. The second will be an analysis of MI patients and two sets of controls (unaffected relatives and population) using conditional logistic regression to find out if apo(a) alleles confer a risk for MI beyond their influence on Lp(a) levels. The third will be a variance components analysis of families of MI patients to quantify the effect of apo(a) gene on Lp(a) levels in these families. This analysis will show if Lp(a) levels are explained to the same extent by the apo(a) gene in families enriched for MI as in healthy families. The study shall be performed on families from the Tyrol. This population has been analyze by us in depth for Lp(a) levels as well as for apo(a) polymorphisms. Thus the distribution of Lp(a) levels, the frequencies of apo(a) size alleles as well as the effect of the apo(a) gene on Lp(a) concentrations are well documented which is a prerequisite for this study.

The project GeRMIT (Genetic Risk Factors for Myocardial Infarction in the Tyrol) had the objective to study genetic risk factors in the Tyrol. Two different study design have been chosen; first a family study in which MI patients were compared with first degree relatives and secondly a case-control study in which the same patients were compared with age and sex matched controls from the same geographic region. To do this study two positions were applied for, one for a MD who had the duty of proband recruitment and sample collection and secondly for a technician to make the labwork. Only one position was granted which was used for the MD to get the project started. During the course of this project samples of 154 MI patients and 248 relatives have been drawn, aliquotized and frozen. Recently the collection of samples from the control population has commenced. Al the collected samples shall be analyzed in a follow up project which is on the way.