VARIANT-SEQUENCE TRANSTHYRETIN (ISOLEUCINE-122) IN LATE-ONSET CARDIACAMYLOIDOSIS IN BLACK-AMERICANS

Background After the age of 60, isolated cardiac amyloidosis is four t imes more common among blacks than whites in the United States; 3.9 pe rcent of blacks are heterozygous for an amyloidogenic allele of the no rmal serum carrier protein transthyretin in which isoleucine is substi tuted for valine at position 122 (Ile 122). We hypothesized that the h igh prevalence of transthyretin lie 122 is at least partially responsi ble for the increased frequency of senile cardiac amyloidosis among bl acks. Methods Paraffin blocks of cardiac tissue were obtained from an earlier study of 52,370 autopsies in Los Angeles and were examined by immunohistochemical and DNA analyses. Samples were available from 32 o f 55 blacks and 20 of 78 whites over 60 years of age with isolated car diac amyloidosis and from two control groups (228 cases). Results Tran sthyretin amyloidosis was identified in 31 of the 32 cardiac-tissue sa mples from the black patients and in 19 of the 20 samples from the whi te patients. Six of the 26 analyzable DNA samples (23 percent) from th e black patients and none of the 19 samples from the white patients we re heterozygous for the lie 122 variant, Four of 125 DNA samples obtai ned at autopsy (3.2 percent) from a second, more recent, age-matched c ohort of blacks without amyloidosis at the same institution were heter ozygous for the transthyretin lie 122 allele. On reexamination the car diac tissue from these four patients contained small amounts of amyloi d not detected at the initial autopsies. All subjects with the lie 122 variant had ventricular amyloid. Conclusions The assessment of elderl y black patients with unexplained heart disease should include a consi deration of transthyretin amyloidosis, particularly that related to th e lie 122 allele. (C)1997, Massachusetts Medical Society.