Mutations in
mitochondrial DNA (
mtDNA) have been associated with
hypertension in several pedigrees with maternal inheritance. However, the pathophysiology of maternally inherited
hypertension remains poorly understood. We reported here clinical, genetic evaluations and molecular analysis of
mtDNA in a three-generation Han Chinese family with
essential hypertension. Eight of 17 matrilineal relatives exhibited a wide range of severity in
essential hypertension, whereas none of the offsprings of the affected father had
hypertension. The age-at-onset of
hypertension in the maternal kindred varied from 31 to 65 years, with an average of 52 years. Sequence analysis of
mtDNA in this pedigree identified the known homoplasmic 4435A>G mutation, which is located at immediately 3' end to the
anticodon, corresponding to the conventional position 37 of
tRNA(Met), and 41 variants belonging to the Asian haplogroup G2a1. In contrast, the 4435A>G mutation occurred among
mtDNA haplogroups B5a, D, M7a2 and J. The
adenine (A37) at this position of
tRNA(Met) is extraordinarily conserved from bacteria to human mitochondria. This modified A37 was shown to contribute to the high fidelity of
codon recognition, structural formation and stabilization of functional tRNAs. However, 41 other
mtDNA variants in this pedigree were the known polymorphisms. The occurrence of the 4435A>G mutation in two genetically unrelated families affected by
hypertension indicates that this mutation is involved in
hypertension. Our present investigations further supported our previous findings that the 4435A>G mutation acted as an inherited risk factor for the development of
hypertension. Our findings will be helpful for counseling families of maternally inherited
hypertension.