Finnish Genetic Data Give Clues to Myocardial Infarction

Approximately 20-30 families founded the Eastern Finnish population in the 1500s. Since then the group has been isolated by factors such as culture, language, religion, and geography, resulting in a population of very high genetic homogeneity. Accurate land records (for tax purposes) and comprehensive church records of births, deaths, marriages, and moves are available from the early 1500s. Since the 1920s, Finland has used standardized state health records, which have been computerized with social security identification from 1970 onwards. The country has high-quality medical care and information systems, ensuring accurate disease diagnosis and prognostic information. Study variables are also reduced by virtue of the fact that factors such as eating habits are very similar throughout the Finnish population.

One cohort derived from the Eastern Finnish population, the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) has been followed since 1984. Over 6,000 phenotypic measurements have been made for each of the more than 3,000 subjects. The resulting medical, genetic, behavioral, and social information are included in one of the world's most comprehensive data banks. The KIHD may be the only prospective cohort in the world that has been followed long enough to enable the study of disease progression and drug responses.

The Finnish biotechnology company Jurilab (Kuopio, Finland; www.jurilab.com) has used its proprietary hierarchical phenotype-targeted sequencing (HPTS) technology to survey the KIHD group for genes linked to AMI. Using this method, candidate genes are selected on the basis of their patho-physiologic role. Specific phenotypic measurements that reflect the expression of these genes, such as enzyme activity, are measured. DNA samples are taken from those subjects with extreme phenotypes (e.g. complete lack of enzyme activity) and are sequenced to find new variations, most of which are single nucleotide polymorphisms (SNPs). Any new SNPs discovered are then typed in the entire population sample and their association with the incidence of multiple diseases and drug effects are analyzed. Finally, family studies are conducted to confirm any SNP/disease associations.

Results of the study, which were released by Jurilab on August 9, 2004, re-affirmed the identity of the majority of genes previously known to be associated with AMI and pinpointed new genes including some that appear to give humans strong protection against coronary disease.

"These discoveries open up a new chapter in the development of predictive tests and much improved therapeutics for coronary heart disease,” said Professor Jukka T. Salonen, Jurilab's CSO. "We are in the process of carrying out similar studies in our main focus areas of cardiovascular and metabolic diseases.”



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