Abstract
Hypertension and stroke are multifactorial disease and both genetic and environmental factors, correlating with each other, are involved in the pathogenesis of them. We collaborated with two large cohort studies (the Suita Study and the Ohasama Study) and examined the genetic involvement of several candidate genes for the risk of hypertension or cardiovascular complications and interaction with environmental factors. These investigations revealed a small but certain effect of gene polymorphism on disease susceptibility under specific environmental conditions as folllows. Homozygous deletion alleles of angiotensin converting enzyme gene (ACE/DD) was associated only with male hypertension, and a polymorphism of endothelin 1 gene increased the genetic predisposition to hypertension only in obese subjects. The positive blood pressure lowering effect of epsilon 4 allele of apolipoprotein E in hypertension risk was observed in young but not in old subjects. We also revealed a unique association between blood pressure variation and angiotensinogen and alpha-adducin gene polymorphism, which suggests the involvement of this polymorphism in the salt sensitivity. In addition, C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene increased risk for hypertension and carotid atherosclerosis in Japanese females and the association was modified by smoking. Our results suggest the importance of interactions between environment and genetics, and the possibility that patient lifestyle modification instructions by physicians and counselors to optimize their environmental factors may be made specific to their genetic information in the future.
