Elsevier

American Heart Journal

Volume 158, Issue 4, October 2009, Pages 607-614
American Heart Journal

Clinical Investigation
Genetics
Cardiac amyloidosis in African Americans: Comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis

https://doi.org/10.1016/j.ahj.2009.08.006Get rights and content

Background

Transthyretin (TTR) mutations known to cause cardiac amyloidosis include V122I, found almost exclusively in African Americans at a prevalence of 3-3.9%. This retrospective study describes TTR V122I–associated cardiac amyloid disease (ATTR) in a major amyloid referral clinic population.

Methods

Self-identified African Americans with amyloidosis (n = 156) were screened for TTR V122I by serum isoelectric focusing; mutant TTR was confirmed by DNA sequencing or mass spectrometry. Cardiac findings in ATTR V122I and immunoglobulin light chain (AL) amyloidoses were compared.

Results

TTR V122I was identified in 36/156 (23.1%) of evaluated patients and included 5 homozygotes; the allele frequency was 0.013. One compound heterozygote (F44L/V122I) and 4 patients who had AL and the mutant TTR allele were characterized. In patients negative for V122I, AL was the most frequent diagnosis (86/120). Cardiomyopathy was present in 100% of patients with ATTR and 84% of patients with AL (P = .01). In patients with dominant cardiac involvement, better survival occurred in ATTR (n = 30) compared to AL (n = 31), (27 vs 5 months, P < .01) although the mean age in ATTR was higher (70.3 vs 56.2 years, P < .01). Congestive heart failure symptoms and electrocardiographic findings were similar in ATTR and AL, but significant differences in echocardiographic measurements were observed.

Conclusions

ATTR V122I and AL are equally prevalent as the cause of cardiomyopathy in African Americans referred for a diagnosis of amyloidosis. Available therapy for AL underscores the need for early and accurate determination of amyloid type.

Section snippets

Patients

Patients who reported their ethnicity as African American and were seen between 1985 and 2009 in the Amyloid Clinic at Boston Medical Center were included. Informed consent for data and sample collection was obtained from patients with the approval of the Boston University Medical Campus Institutional Review Board. Clinical data included history, physical examination and laboratory studies of hematologic parameters and organ function. Tests for a plasma cell dyscrasia occurring in AL included

Identification of TTR V122I

Between 1985 and 2009, 156 African Americans (Figure 1) were evaluated for a diagnosis of amyloidosis. In 3 patients, amyloid disease could not be confirmed. Sera were tested for a TTR variant by IEF. Normally, one protein band corresponding to wild-type, monomeric TTR is detected; the occurrence of 2 protein bands indicates a variant TTR is present. We and others have previously shown that V122I has a lower pI than wild-type TTR (Figure 2, A).14, 18 In the present study, IEF screening

Discussion

This is the first report of a large series of African American patients with biopsy-confirmed amyloidosis and inheritance of TTR V122I. The study was designed to evaluate the occurrence of V122I and resulting ATTR in African Americans in a referral population. Although it is important to note that TTR V122I mutation carriers were identified retrospectively from blood samples in an amyloid clinic, the results show that the TTR V122I mutation was present in more than one fifth (36/156) of African

Acknowledgements

The authors are grateful to Pamela SooHoo and Brian Spencer for their excellent technical assistance.

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