High specificity makes DNA screening the method of choice for diagnosis of familial hyper-cholesterolaemia

No Abstract

Editorial

High specificity makes DNA screening the method of choice for diagnosis of familial hypercholesterolaemia

Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population

Objective. Familial hypercholesterolaemia (FH) is a common genetic disease characterised by strikingly elevated. plasma cholesterol concentration, which can lead to premature coronary death if left untreated. In this study DNA diagnosis of FH, which allows detection before onset of clinical symptoms, was evaluated against biochemical parameters routinely used to identify subjects with FH.Design. A population-based strategy was used to identify low-density lipoprotein receptor (LDLR) gene defects in South Africans with clinical signs of FH, followed by a family-based DNA screening approach for presymptomatic diagnosis of FH.Results. DNA screening of 790 at-risk relatives for the FHrelated mutations identified in 379 index cases, allowed accurate disease diagnosis in an additional 338 relatives and exclusion of the relevant mutation in 452 individuals. The sensitivity and speeifidty of the diagnosis, based on total cholesterol values measured in family members of FH heterozygous index cases with one of the three founderrelated mutations, D154N, D206E and V408M, were 89.3% and 81.9%, respectively.Conclusion. The predominance of 10 LDLR gene mutations in the local population justifies population-directed D A diagnosis of FH in South Africa on a routine basis, particularly since expression of the defective gene measured in biochemical tests does not allow accurate diagnosis of FH in all cases. D A testing provides a definitive tool for family tracing aimed at pre-clinical diagnosis and preventive treatment of FH

Clinical versus molecular diagnosis of heterozygous familial hypercholesterolaemia in the diverse South African population

No Abstract

Rapid thrombophilia genetic test facilities improved prenatal care for mohter and child

No Abstract. South African Family Practice Vol. 47(7) 2005: 50-5

Fat Mass and Obesity-Associated (FTO) Gene Polymorphisms Are Associated with Physical Activity, Food Intake, Eating Behaviors, Psychological Health, and Modeled Change in Body Mass Index in Overweight/Obese Caucasian Adults

The fat mass and obesity-associated (FTO) gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085–rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed from whole blood samples. Weight and height was measured and a non-quantified food frequency questionnaire was completed to assess food group intake. Validated questionnaires were completed to assess physical activity (Baecke questionnaire), psychological health (General Health questionnaire, Rosenburg self-esteem scale and Beck Depression Inventory), and eating behavior (Three Factor Eating questionnaire). The risk alleles of the FTO polymorphisms were associated with poorer eating behaviors (higher hunger, internal locus for hunger, and emotional disinhibition scores), a higher intake of high fat foods and refined starches and more depressive symptoms. The modeled results indicate that interactions between the FTO polymorphisms or haplotypes and eating behavior, psychological health, and physical activity levels may be associated with BMI. The clinical significance of these results for implementation as part of weight management interventions needs further investigation

A view on genomic medicine activities in Africa: Implications for policy

Genomics policy development involves assessing a wide range of issues extending from specimen collection and data sharing to whether and howto utilize advanced technologies in clinical practice and public health initiatives. A survey was conducted among African scientists and stakeholders with an interest in genomic medicine, seeking to evaluate: 1) Their knowledge and understanding of the field. 2) The institutional environment and infrastructure available to them. 3) The state and awareness of the field in their country. 4) Their perception of potential barriers to implementation of precision medicine

Editorial : Implementation of genomic medicine in Africa : one continent, one vision

The translation of genetic research from bench to bedside involves multiple choices related to clinician-patient shared decision-making, with ethical implications at every step of the way. Given the evolving evidence base and limited genomic data from African genomes, we were delighted to receive three reviews, one opinion article, three perspectives, six original papers, and a brief research report with a checklist for assessment of the readiness to implement public health genomics. The latter contribution by Jongeneel et al. included survey results previously generated in parallel to the development of a framework for implementation of genomic medicine in Africa, which was published in February 2021 on commission of the African Academy of Sciences (https://www.aasciences.africa/publications/policy-paper-frameworkimplementation- genomic-medicine-public-health-africa). The Policy Brief summarized this framework for personalized genomic medicine as the foundation of the current translational Research Topic, showcasing collated evidence of applied knowledge in Africa to enable translation of research into clinical practice, as the study endpoint. The wide range of methodologies used, and implementation approaches presented, were evaluated for evidence of transition from population to individualised risk stratification required for the application of personalised genomic medicine.http://www.frontiersin.org/Geneticsam2024School of Health Systems and Public Health (SHSPH)Non

Familial defective apolipoprotein-B is rare in hypercholesterolaemic South African Afrikaners, coloureds and Indians

No Abstract

APRI: A simple bedside marker for advanced fibrosis that can avoid liver biopsy in patients with NAFLD/NASH

Background. Non-alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. The NASH fibrosis score (NFS) has proven to be a reliable, non-invasive marker for prediction of advanced fibrosis. Aspartate aminotransferase-to-platelet ratio index (APRI) is a simpler calculation than NFS, but has never been studied in patients with non-alcoholic fatty liver disease (NAFLD). Aim. To validate APRI as a non-invasive marker of liver fibrosis in subjects with NAFLD to be used in clinical practice. Design/Methods. The cohort consisted of 111 patients with histological diagnoses of NAFLD. The biopsy samples were staged and graded according to the NASH clinical research network (CRN) criteria. These were grouped into fatty liver disease (FLD), NASH, no/mild fibrosis, and advanced fibrosis. The sensitivity and specificity of APRI were compared with NFS and aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratio. Results. The APRI was significantly higher in the advanced fibrosis group. The area under receiver operating characteristic (ROC) curve for APRI was 0.85 with an optimal cut-off of 0.98, giving a sensitivity of 75% and a specificity of 86%. The NFS was significantly lower in the advanced fibrosis group. The ROC for NFS gave an area under curve (AUC) of 0.77 and a cut-off value of -1.3 with a sensitivity of 76% and specificity of 69%. The positive predictive value for APRI was 54% as opposed to 34% for NFS. The negative predictive value was 93% for APRI and 94% for NFS. Conclusion. APRI compared favourably to NFS and was superior to AST/ALT for the prediction of advanced fibrosis. We therefore propose the use of APRI in a new algorithm for the detection of advanced fibrosis