Genetic risk factors for cerebral infarction using data from a large‐scale genetic epidemiological study: the Ohasama Study

Background: With the imminent advent of an extremely aged society, there will be an increasing requirement for the prediction, early detection and treatment of cerebral infarction. Involved in the etiological mechanisms of cerebral infarction are a number of complex genetic and environmental factors related to the onset and progression of hypertension and arteriosclerosis. Elucidation of the significance of the various risk factors will require definite identification of phenotypes using large numbers of subjects. Methods: The present study was conducted as part of a cohort study with subjects from the general population of a rural community (the Ohasama Study). Blood pressure (BP) patterns were assessed through random home‐based and clinical measurements, as well as 24 h ambulatory BP monitoring. Magnetic resonance imaging of the brain was carried out in some subjects in order to detect asymptomatic cerebral infarcts, the maximum intima–media thickness was determined by carotid high‐resolution ultrasonography, and cognitive function was assessed using the mini mental state examination. Correlation analysis of these parameters and the candidate hypertensive genotypes was then performed. Results: Significant associations were seen between (i) gene polymorphisms in the renin–angiotensin system and asymptomatic cerebral infarction and the non‐dipper pattern of circadian blood pressure variation; and (ii) endothelial nitric oxide synthase (eNOS) gene polymorphism and arterial pressure, lacunar score and cognitive function. An association was seen between the endothelin‐1 polymorphism and hypertension, but only in obese subjects. Conclusion: There are interactions between genes and the environment in the etiology of cerebral infarction.