LDLR Gene Mutation p.Asp360His and Familial Hypercholesterolemia in a Mexican Community.
Arch Med Res
; 51(2): 153-159, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-32113782
BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by an increased LDL-cholesterol (LDLc) serum concentration and premature cardiovascular disease. Screening of small populations where at least one homozygous (HoFH) patient has been identified may be a proper approach for detecting FH patients. Previously, we reported an HoFH patient carrying the mutation p.Asp360His LDLR, who was born in the Mexican community El Triunfo (Quimixtlan, Puebla). AIM OF THE STUDY: To identify patients with familial hypercholesterolemia in the community El Triunfo and to describe their clinical and biochemical characteristics. METHODS: We studied 308 individuals by quantifying lipid levels and by DNA sequencing. RESULTS: Sixteen of 308 individuals presented an LDLc level >170 mg/dL and all of them turned out to be heterozygous for the LDLR p.Asp360His variant. Subsequently, 34 of their first-degree relatives (mainly siblings and parents) were genotyped rendering six additional HeFH patients, which resulted in 22 carriers of the mutated allele. The study of six LDLR polymorphisms in four unrelated individuals from the community (one HoFH and three HeFH) showed the same haplotype combination, suggesting a unique ancestral origin of the mutation. CONCLUSIONS: The community El Triunfo, has the highest worldwide frequency ever reported of HeFH, with 7.14% (22/308, equivalent to 1/14 inhabitants). Since the HeFH patients showed variable biochemical expression, we suggest looking for factors with the potential to modify the phenotype. Finally, we stress the importance of establishing accurate LDLc cut-off points applicable to Mexican population for the diagnosis of FH.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de LDL
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Hiperlipoproteinemia Tipo II
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LDL-Colesterol
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Mexico
Idioma:
En
Revista:
Arch Med Res
Assunto da revista:
MEDICINA
Ano de publicação:
2020
Tipo de documento:
Article
País de publicação:
Estados Unidos