The role of DNA methylation in hypertension

Abstract

DNA methylation is the covalent modification of DNA that affects its function, without altering DNA sequences. Three important roles of DNA methylation include intrauterine programming, acquired predisposition, and transgenerational inheritance. A wide variety of factors can affect DNA methylation. Intrauterine programming involves drastic changes in DNA methylation patterns during cellular development and differentiation, which have a long-lasting effect on the predisposition of offspring. Influences from the mother, including maternal nutritional status, modify intrauterine epigenetic programming. In contrast to the rapid and drastic changes in utero, postnatal factors in daily life can also continue to slowly and dynamically change DNA methylation patterns in both somatic and germ cells. Epigenetic changes occurring in germ cell DNA exert a transgenerational impact on the phenotype of future generations, thus providing a means for ancestral transmission of environmental experiences. Despite adaptive ability, mismatch effect of transgenerational inheritance could be potentially harmful to health if environment has changed, and the acquired acclimatization is no longer beneficial. Increasing evidence from both human and animal studies indicates that DNA methylation exerts a causal impact on the development of hypertension. Therefore, an adverse outcome of maternal malnutrition could be the development of hypertension in offspring, whereby nutritional factors or disease conditions could induce phenotypes susceptible to hypertension through alteration of DNA methylation patterns. These factors are likely to alter DNA methylation patterns in all tissues including germ cells, and despite no direct evidence of an association between transgenerational epigenetic inheritance and hypertension, it is likely to play a role.