Percorrer por autor "Mariano, C."
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- Applicability of the low-density lipoprotein cholesterol gene score in a south European populationPublication . Mariano, C.; Futema, M.; Humphries, S.E.; Bourbon, M.Aim: The correct identification of the dyslipidaemia is of great importance in order to implement specific interventions, especially for cardiovascular disease (CVD) prevention. The Global Lipids Genetics Consortium (GLGC) reported 158 loci associated with lipid traits, by genome-wide association studies (GWAS), although practical value of GWAS approach is still a subject of debate, half of these loci are previously known to influence serum lipid concentrations. Previous studies (Talmud et al., 2013; Futema et al., 2015) have demonstrated that the co-inheritance of low-density lipoprotein (LDLC)-raising alleles from 6 of these SNPs is associated with the Familial Hypercholesterolaemia (FH) phenotype. Here we investigated the applicability of the LDL-C genetic risk score in the Portuguese FH population.
- FH Phenotype: monogenic, polygenic and other causesPublication . Mariano, C.; Alves, A.C.; Medeiros, A.M.; Chora, J.R.; Futema, M.; Humphries, S.E.; Bourbon, M.Familial Hypercholesterolaemia (FH) is a monogenic lipid disorder caused by mutations in LDLR, APOB, and PCSK9 genes. However, 50% of individuals with clinical diagnosis of FH do not have a mutation in one of these three genes, so other causes for their phenotype must exist. The FH phenotype has been associated recently to other monogenic disorders as lysosomal acid lipase deficiency (LALD) and sitosterolaemia or can have a polygenic origin. The aim of this work was to characterize the origin of the FH phenotype in a cohort of patients with clinical diagnosis of FH.
- Lysosomal acid lipase deficiency: a hidden disease among cohorts of familial hypercholesterolemia?Publication . Chora, J.R.; Alves, A.C.; Medeiros, A.M.; Mariano, C.; Lobarinhas, G.; Guerra, A.; Mansilha, H.; Cortez-Pinto, H.; Bourbon, M.Highlights: - Dyslipidemia phenotype of patients with familial hypercholesterolemia and lysosomal acid lipase deficiency (LALD) can overlap; - Familial hypercholesterolemia negative patients should be investigated to identify possible LALD patients; - Correct identification of LALD patients is important for patient prognosis. Background: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder and an unrecognized cause of dyslipidemia. Patients usually present with dyslipidemia and altered liver function and mutations in LIPA gene are the underlying cause of LALD. Objective: The aim of this study was to investigate LALD in individuals with severe dyslipidemia and/or liver steatosis. Methods: Coding, splice regions, and promoter region of LIPA were sequenced by Sanger sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH) patients (n = 492) and in a population sample comprising individuals with several types of dyslipidemia and/or liver steatosis (n = 258). Results: This study led to the identification of LALD in 4 children referred to the Portuguese FH Study, all with a clinical diagnosis of FH. Mild liver dysfunction was present at the age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults at the time of referral have been identified with LALD. Conclusion: LALD is a life-threatening disorder, and early identification is crucial for the implementation of specific treatment to avoid premature mortality. FH cohorts should be investigated to identify possible LALD patients, who will need appropriate treatment. These results highlight the importance of correctly identifying the etiology of the dyslipidemia.
- The applicability of the low-density lipoprotein cholesterol gene score in the Portuguese populationPublication . Mariano, C.; Futema, M.; Humphries, S.E.; Bourbon, M.Aim: The correct identification of the dyslipidaemia is of great importance in order to implement specific interventions, especially for cardiovascular disease (CVD) prevention. The Global Lipids Genetics Consortium (GLGC) reported 158 loci associated with lipid traits, by genome-wide association studies (GWAS), although practical value of GWAS approach is still a subject of debate, half of these loci are previously known to influence serum lipid concentrations. Previous studies (Talmud et al., 2013; Futema et al., 2015) have demonstrated that the co-inheritance of low-density lipoprotein (LDL-C)-raising alleles from 6 of these SNPs is associated with the Familial Hypercholesterolaemia (FH) phenotype. Here we investigated the applicability of the LDL-C genetic risk score in the Portuguese FH population.
- The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causesPublication . Mariano, C.; Alves, A.C.; Medeiros, A.; Chora, J.R.; Antunes, M.; Futema, M.; Humphries, S.E.; Bourbon, M.Familial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management.
- The FH phenotype: monogenic familial hypercholesterolaemia, polygenic dyslipidaemia and other causesPublication . Mariano, C.; Medeiros, A.M.; Alves, A.C.; Chora, J.R.; Futema, M.; Humphries, S.E.; Antunes, M.; Bourbon, M.Introduction: (i) Cardiovascular disease (CVD), particularly coronary heart disease (CHD) and stroke, are the leading cause of morbidity and mortality worldwide; (ii) Dyslipidaemia is an important but modifiable cardiovascular risk factor. For instance, Familial Hypercholesterolaemia (FH) is a monogenic autosomal condition where patients present very high LDL-C values and an increase cardiovascular risk; (iii) FH is caused by mutations in 3 genes: LDLR, APOB and PCSK9. However in only about 40%-50% of the cases an FH causing mutation is found.
- The FH phenotype: monogenic familial hypercholesterolaemia, polygenic dyslipidaemia and other causesPublication . Mariano, C.; Antunes, M.; Medeiros, A.M.; Alves, A.C.; Futema, M.; Humphries, S.E.; Bourbon, MafaldaFamilial hypercholesterolaemia (FH) is a monogenic autosomal condition where patients present very high LDL-C values and an increase cardiovascular risk. FH is caused by mutations in 3 genes: LDLR, APOB and PCSK9. However in only about 40%-50% of the cases an FH causing mutation is found. The FH phenotype has been associated recently to other monogenic disorders as lysosomal acid lipase deficiency or can have a polygenic origin. The aim of this work was to characterize the origin of FH phenotype in a cohort of patients with a clinical diagnosis of FH.
- Will Familial Hypercholesterolaemia Cohorts Hide Many More Lisosomal Acid Lipase Deficiency Patients?Publication . Chora, J.R.; Alves, A.C.; Medeiros, A.M.; Mariano, C.; Lobarinhas, G.; Guerra, A.; Mansilha, H.; Bourbon, MafaldaAims: Lisosomal Acid Lipase Deficiency (LALD), historical known as Cholesterol Ester Storage Disease (CESD), is an autosomal lisosomal storage recessive disorder and an unrecognized cause of dyslipidaemia. Mutations in LIPA gene are the underlying cause of LALD, being a mutation in the splice site of exon 8 the most common cause of the disease. Patients with LALD present dyslipidaemia and altered liver function. The aim of this work was to analyze LIPA gene in patients with unexplained dyslipidaemia.