LDLR Gene Mutation p.Asp360His and Familial Hypercholesterolemia in a Mexican Community
| Autor: | Norma Alejandra Vázquez Cárdenas, María Teresa Magaña Torres, Sergio Yair Rodríguez Preciado, Juan Ramón González García, Teresita De Jesús Hernández Flores, Ana Gabriela Colima Fausto, Yoaly Josefina Sánchez López |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male Adolescent Familial hypercholesterolemia Disease Hyperlipoproteinemia Type II 03 medical and health sciences Young Adult 0302 clinical medicine medicine Humans Allele Child Mexico Aged Genetics Aged 80 and over business.industry Haplotype Autosomal dominant trait General Medicine Cholesterol LDL Middle Aged medicine.disease Phenotype 030104 developmental biology Receptors LDL 030220 oncology & carcinogenesis Child Preschool Mutation (genetic algorithm) LDL receptor Mutation Female business |
| Zdroj: | Archives of medical research. 51(2) |
| ISSN: | 1873-5487 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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