TTR V122I allele in Afro-Caribbeans and Cardiovascular Disease V1.2
Research type
Research Study
Full title
A study to determine the gene frequency of TTR V122I allele in Afro-Caribbean Patients with Cardiovascular Disease
IRAS ID
149451
Contact name
Lisa Anderson
Contact email
Sponsor organisation
St George's University of London
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Biopsy confirmed TTR V122I cardiac amyloid is the underlying cause for heart failure in 10% of the Afro-Caribbean heart failure population at St George's Hospital and at least 6% of the newly diagnosed heart failure patients at King's Hospital.
In 1996, an epidemiological study demonstrated the V122I allele in 65 of 1688 Black Americans, giving a calculated allele carrier rate of 3.9% in the United States, yet the clinical implication of this finding was not known at the time. The allele was later detected in 10.3% of an African-American cohort over 60 years of age taking part in a large heart failure trial. Despite extensive screening of other populations, this mutation is almost exclusively present in persons of African ancestry.
The aim of this study is to establish the frequency of the TTR V122I allele in Afro-Caribbean patients with cardiovascular disease and compare it with that of the healthy Afro-Caribbean population. Our hypothesis is that TTR V122I carrier frequency is higher in the disease cohorts outlined and that it is, in fact, a risk allele predicting cardiovascular disease.
Lay summary of study results: We have demonstrated an almost 4 times concentration of the V142I allele in the black HF population (14%) versus the healthy black population (3.6%) indicating that V142I carrier status is associated with significantly increased risk for the development of heart failure. We have also demonstrated that the dominant phenotype for 72% of black HF patients V142I carriers was V142I ATTR-Cardiomyopathy. These are important findings given the frequency of the allele in the UK Black population (3.6% equivalent to 86,400 people in the UK). In addition, we have re-affirmed available data indicating gender- and age dependent penetrance underlining the importance of regular follow-up and rescreening for Black individuals with the V142I variant as they age, even if the initial presentation is not consistent with ATTR- Cardiomyopathy.REC name
London - Queen Square Research Ethics Committee
REC reference
15/LO/0442
Date of REC Opinion
26 May 2015
REC opinion
Further Information Favourable Opinion