Maternal Influence on the Inheritance of Hypertension
Genetic determinants of essential hypertension remain poorly understood. To date, the focus of molecular genetic research has been primarily on the nuclear genes, whereas the role of the mitochondrial genome has not been ascertained. Although mitochondrial genome is just 16.5 kilobase pairs in length and comprises less than 1% of the total nucleic acid content in mammalian cells, mitochondria occupy pivotal position in human cellular bioenergetics, and mitochondrial defects have been implicated in a wide spectrum of human genetic disorders. In contrast to nuclear inheritance, mitochondrial genome is inherited exclusively through the mother. To assess the relative maternal and paternal contributions to the familial aggregation of hypertension, we examined family history data obtained from 310 hypertensive probands (65 African American, 149 US Caucasian, 96 Greek Caucasian) ascertained without respect to parental hypertension status. Proportions of affected mothers and fathers were compared using a χ2test. Cumulative lifetime risk for hypertension in mothers and fathers was estimated using a maximum likelihood extension of Kaplan Meier survival analysis. We found that the proportion of hypertensive mothers was significantly greater than the proportion of hypertensive fathers in all three ethnic groups. The proportions of hypertensive mothers were 83.9, 63.2 and 83.3% for African Americans, US Caucasians and Greek Caucasians, respectively. In contrast, the observed proportions for fathers were, respectively, 53.2, 47.3 and 48.8%. In conclusion, we observe a consistent maternal component in the inheritance of hypertension in three ethnic groups. Although environmental and epigenetic influences can not be excluded, our findings provide a new dimension in the search for the genetic components of hypertension and suggest that hypertension may prove to be not only polygenic but also “polygenomic” disorder. Furthermore, our data indicate that when assessing a patient’s risk for hypertension, particular attention should be paid to the maternal portion of the family history.