High Prevalence of Primary Dyslipidaemia in Black South African Patients at a Tertiary Hospital in Northern Gauteng; South Africa

BACKGROUND:The prevalence of cardiovascular disease is projected to be 38.7% for the USA in 2020; including coronary heart disease at 8.6% and stroke at 3.6%. In South Africa (SA); premature deaths due to heart and blood vessel diseases in people of working age (35 - 64 years) have been predicted to increase by 41% between 2007 and 2030; with enormous negative economic impact. Atherosclerosis underlies much of the pathogenesis; which involves risk factors including dyslipidaemia. Secondary dyslipidaemia associated with diabetes mellitus; hypothyroidism; chronic renal disease; cholestasis; nephrotic syndrome; alcohol excess; drugs such as thiazide diuretics and antiretroviral agents may respond to treatment of underlying causes; but residual dyslipidaemia may in such cases be due to primary disorders of metabolism. Primary dyslipidaemias are uncommon and to a large extent underdiagnosed; especially in the black population of SA; reflecting a lack of clinical and laboratory awareness or expertise. Specific diagnoses enable effective intervention in the patients as well as the families.OBJECTIVE:To assess the burden and prevalence of dyslipidaemia in the SA black population at Dr George Mukhari Hospital in the north region of Gauteng.METHOD:A retrospective data analysis of 12-month lipid profiles comprising triglyceride (TG); total cholesterol (TC); high-density lipoprotein cholesterol and directly measured low-density lipoprotein (LDL) cholesterol (LDLC).RESULTS:There were 24 656 requests for 6 348 patients. The lipid cut-off levels were somewhat arbitrary but were based on the commonly used decision-making levels in the treatment guidelines. Severe hypercholesterolaemia (etgt;7 mmol/L) was seen in 299 (4.7%) patients and extreme hypercholesterolaemia (etgt;12 mmol/L) was seen in 30 (0.5%) patients. LDLC (etgt;5 mmol/L) occurred in 80 (1.3%) patients and etgt;10 mmol/L in 19 (0.3%) patients. A predominant triglyceride problem was seen in 578 (9.1%) patients with TG (etgt;2 mmol/L) and TC (etlt;5 mmol/L); whereas moderate hypertriglyceridaemia (etgt;5 mmol/L) was present in 113 (1.8%) patients; and more severe hypertriglyceridaemia (etgt;10 mmol/L) in 10 (0.2%). TC (etgt;5 mmol/L) with LDL (etgt;3 mmol/L) but TG in the normal range was seen in 369 (5.8%) patients; indicating a cholesterol-predominant problem. In contrast; LDLC (etgt;3 mmol/L) and TG (etgt;1.7 mmol/L) was seen in 249 (3.87%) representing mixed hyperlipidaemia. Paediatric patients with severe dyslipidaemia mostly suffered from nephrotic syndrome.CONCLUSION:A significant burden and a high prevalence of dyslipidaemias were present in adults in whom a monogenic disorder should be considered. The extent and severity of dyslipidaemia justify a special clinic and laboratory to ensure accurate diagnosis with effective intervention for patients and their families

Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews.

G197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on disease expression. Index cases from Israel (n=46), South Africa (n=24), Russia (n=7), The Netherlands (n=1), and the United States (n=1) were enlisted. All trace their ancestry to Lithuania. A highly conserved haplotype (D19S221:104-D19S865:208-D19S413:74) was identified in G197del chromosomes, suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the deletion was found to be 20 +/- 7 generations (the 95% confidence interval is 15-26 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 14th century. This corresponds with the founding of the Jewish community of Lithuania (1338 a.d.), as well as with the great demographic expansion of AJ individuals in eastern Europe, which followed this settlement. The penetrance of mutation-linked severe hypercholesterolemia is high (94% of heterozygotes have a baseline concentration of LDL cholesterol (LDL-C) that is >160 mg/dl), and no significant differences in the mean baseline lipid level of G197del carriers from different countries were found. Polymorphisms of apolipoprotein E and of scavenger-receptor class B type I were observed to have minor effects on the plasma lipid profile. With respect to determinative genetic influences on the biochemical phenotype, there is no evidence that could support the possibility of a selective evolutionary metabolic advantage. Therefore, the founder effect in a rapidly expanding population from a limited number of families remains a simple, parsimonious hypothesis explaining the spread of G197del-LDLR-linked FH in AJ individuals.