| Revista: | Genetics and molecular biology |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000420004 |
| ISSN: | 1415-4757 |
| Autores: | Idrees, Muhammad1 Siddiq, Abdul Rauf1 Ajmal, Muhammad1 Akram, Muhammad1 Khalid, Rana Rehan1 Hussain, Alamdar1 Qamar, Raheel1 Bokhari, Habib1 |
| Instituciones: | 1COMSATS Institute of Information Technology, Islamabad. Pakistán |
| Año: | 2018 |
| Periodo: | Sep |
| Volumen: | 41 |
| Número: | 3 |
| Paginación: | 570-577 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Analítico |
| Resumen en inglés | Paraoxonase 1 (PON1) is a serum enzyme associated with high density lipoprotein (HDL) regulation through its paraoxonase and arylesterase activity. PON1 inhibits the oxidation of HDL and low density lipoprotein (LDL), and is involved in the pathogenesis of a variety of diseases including atherosclerosis. Conversely, mutations in the low den - sity lipoprotein receptor ( LDLR ) result in failure of receptor mediated endocytosis of LDL leading to its elevated plasma levels and onset of familial hypercholesterolemia (FH). In the current study we investigated the role of PON1 polymorphisms rs662; c.575A > G (p.Gln192Arg) and rs854560; c.163T > A (p.Leu55Met) in a large family having FH patients harboring a functional mutation in LDLR. Genotypes were revealed by RFLP, followed by confirmation through Sanger sequencing. PON1 activity was measure by spectrophotometry. Our results show significantly reduced serum paraoxonase and arylesterase activities in FH patients compared with the healthy individuals of the family (p < 0.05). PON1 QQ192 genotype showed a significantly higher association with FH (p=0.0002). PON1 Q192 isoform was associated with reduced serum paraoxonase activity by in silico analysis and PON1 R192 exhibited higher serum paraoxonase and arylesterase activity than the other polymorphs. Our results highlight that the combination of LDLR mutations and PON1 MMQQ genotypes may lead to severe cardiac events |
| Disciplinas: | Química, Medicina |
| Palabras clave: | Bioquímica, Endocrinología, Sistema cardiovascular, Paraoxonasa-1, Hipercolesterolemia, Arilesterasa, Mutaciones, Gen LDLR |
| Keyword: | Biochemistry, Endocrinology, Cardiovascular system, Paraoxonase-1, Hypercholesteremia, Arylesterase, Mutations, LDLR gene |
| Texto completo: | Texto completo (Ver PDF) |
