Cascade Screening for Familial Hypercholesterolemia in South Africa: The Wits FIND-FH Program.
Arterioscler Thromb Vasc Biol
; 40(11): 2747-2755, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32878475
ABSTRACT
OBJECTIVE:
Due to gene founder effects, familial hypercholesterolemia (FH) has a prevalence of ≈180 in populations of Afrikaner ancestry and is a major contributor to premature atherosclerotic cardiovascular disease in South Africans of Jewish and Indian descent. No systematic program exists to identify these families. Furthermore, information regarding FH prevalence in Black Africans is sparse. The Wits FIND-FH program was initiated in late 2016 to address these issues. Approach andResults:
Based on index subjects with definite or probable FH, first-degree relatives were contacted, informed consent obtained, and targeted medical history, physical examination, and blood samples collected. In patients with likely FH using the Simon Broome criteria, DNA analysis for LDLR (low-density lipoprotein receptor), APOB (apolipoprotein B), PCSK9 (proprotein convertase subtilisin/kexin type 9), and LDLRAP1 (LDLR adaptor protein 1) variants was analyzed by next-generation sequencing. Of the initial 700 subjects screened of whom 295 (42%) were index cases, 479 (68.4%) were clinically diagnosed with probable or definite FH. Genetic analysis confirmed 285 of 479 (59.5%) as having variants consistent with FH. Three subjects met the clinical diagnosis for homozygous FH, but DNA analysis revealed a further 34 patients, including 4 Black African subjects, with ≥2 FH-causing variants.CONCLUSIONS:
Using phenotype cascade screening, the Wits FIND-FH program has screened an average of 30 subjects monthly of whom 68% had a clinical diagnosis of FH with ≈60% genetically confirmed. The program is identifying a small but growing number of Black South Africans with FH. Interestingly, 37 subjects (7.7%) who underwent DNA testing were found to have ≥2 FH-causing variants.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Receptores de LDL
/
Testes Genéticos
/
Proteínas Adaptadoras de Transdução de Sinal
/
Apolipoproteína B-100
/
Pró-Proteína Convertase 9
/
Hiperlipoproteinemia Tipo II
/
LDL-Colesterol
Tipo de estudo:
Diagnostic_studies
/
Evaluation_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Africa
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article