Variant-Sequence Transthyretin (Isoleucine 122) in Late-Onset Cardiac Amyloidosis in Black Americans

doi:10.1056/NEJM199702133360703

Volume 336:466-473		February 13, 1997		Number 7

Variant-Sequence Transthyretin (Isoleucine 122) in Late-Onset Cardiac Amyloidosis in Black Americans

Daniel R. Jacobson, M.D., Raymond D. Pastore, M.D., Robert Yaghoubian, M.D., Immaculata Kane, M.S., Gloria Gallo, M.D., Francis S. Buck, M.D., and Joel N. Buxbaum, M.D.

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ABSTRACT

Background After the age of 60, isolated cardiac amyloidosisis four times more common among blacks than whites in the UnitedStates; 3.9 percent of blacks are heterozygous for an amyloidogenicallele of the normal serum carrier protein transthyretin inwhich isoleucine is substituted for valine at position 122 (Ile122). We hypothesized that the high prevalence of transthyretinIle 122 is at least partially responsible for the increasedfrequency of senile cardiac amyloidosis among blacks.

Methods Paraffin blocks of cardiac tissue were obtained froman earlier study of 52,370 autopsies in Los Angeles and wereexamined by immunohistochemical and DNA analyses. Samples wereavailable from 32 of 55 blacks and 20 of 78 whites over 60 yearsof age with isolated cardiac amyloidosis and from two controlgroups (228 cases).

Results Transthyretin amyloidosis was identified in 31 of the32 cardiac-tissue samples from the black patients and in 19of the 20 samples from the white patients. Six of the 26 analyzableDNA samples (23 percent) from the black patients and none ofthe 19 samples from the white patients were heterozygous forthe Ile 122 variant. Four of 125 DNA samples obtained at autopsy(3.2 percent) from a second, more recent, age-matched cohortof blacks without amyloidosis at the same institution were heterozygousfor the transthyretin Ile 122 allele. On reexamination the cardiactissue from these four patients contained small amounts of amyloidnot detected at the initial autopsies. All subjects with theIle 122 variant had ventricular amyloid.

Conclusions The assessment of elderly black patients with unexplainedheart disease should include a consideration of transthyretinamyloidosis, particularly that related to the Ile 122 allele.

Source Information

From the Research Service, New York Veterans Affairs Medical Center, New York (D.R.J., R.D.P., R.Y., I.K., J.N.B.); the Departments of Medicine (D.R.J., J.N.B.) and Pathology (G.G., J.N.B.), New York University School of Medicine, New York; and the Department of Pathology, Los Angeles County–University of Southern California Medical Center, Los Angeles (F.S.B.).

Address reprint requests to Dr. Buxbaum at the Research Service, New York Veterans Affairs Medical Center, 423 East 23rd St., New York, NY 10010.

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