Asociace genotypu s nemocí a odhalování jejich prostředím ovlivnitelných příčin: využití principu mendelovské randomizace

Genotype – Disease Association and Possibility to Reveal Environmentally Modifiable Disease Causes: The Use of Mendelian Randomization Principle

Though the methodology and designs of epidemiological studies and analyses of medical databases have improved, associations between modifiable exposures and the disease in observational epidemiological studies remain partly biased. Mendelian randomization principle, which is the random distribution of parental genes to offspring in meiosis during gametogeneis and at conception, represents a chance for methodology of evaluation of the causal relations between the external cause and the disease. The use of this principle assumes the association between the disease and the genetic polymorphism which reflects the biological relation between the suspected exposure and the disease, and is generally less prone to the phenomenon of confounding and reverse causation that can impair the interpretation of results in conventional observational studies. Authors describe explanatory options of the Mendelian randomization principle using examples in folic acid – homocysteine – coronary heart disease, and isothiocyanate versus lung carcinoma. Though the use of Mendelian randomization principle has its limitations, it offers new possibilities to test causal relations and clearly shows that means invested into the Human genome project can contribute to the understanding and prevention of adverse effects of modifiable exposure to the human health.

Key words:
genetic epidemiology, risk factors, causality, folic acid, methylene tetrahydrofolate reductase, homocysteine, coronary heart disease, glutathione-S-transferase, brassica genus, isothiocyanate, lung carcinoma.