Analysis of mutations causing familial hypercholesterolaemia in black South African patients of different ancestry

Background. Familial hypercholesterolaemia (FH) is usually caused by mutations in three genes (LDLR, APOB and PCSK9). Objective. To identify the spectrum of FH-causing mutations in black South African (SA) patients.Methods. DNA samples of 16 unrelated South African FH patients with elevated low-density lipoprotein cholesterol levels, tendon xanthomas and corneal arcus (3 clinically homozygous FH and 13 heterozygous FH) of ethnic African origin were screened for mutations in the LDLR (coding region, promoter and intron/exon boundaries), APOB (part of exon 26) and PCSK9 genes (exon 7), using high-resolution melting.Results. Eight LDLR mutations were identified, for an overall detection rate of 8/19 predicted FH-causing alleles (42.1%). The previously reported six base pair deletion p.(D47_G48del) was found in two patients, and two novel variants (c.1187-25T>C and c.1664T>G p.(L555R)) were found, both predicted to be pathogenic using in silico web-based predictive algorithms. No pathogenic variants in APOB or PCSK9 were found.Conclusions. These findings contribute to the knowledge of allelic heterogeneity in the spectrum of FH-causing mutations in black SA patients, signifying their ancestral diversity. The relatively low overall detection rate may reflect locus heterogeneity of the FH phenotype in black SA FH patients

Interrelationship of growth hormone; glucose and lipid metabolism

BACKGROUND:The relationship between Growth hormone (GH) and the metabolism of glucose and lipid is not completely understood. OBJECTIVE:The present study is to obtain further information that will clarify the relationships between growth hormone and the metabolism of glucose and lipid.METHODS:The subjects were randomly selected 25 male (11) and female (14) healthy individuals aged 35.96 +/- 8.05 years. After an overnight fast (10-12 hours), blood was taken from the subjects into heparinised tubes, centrifuged at 5,000 rpm for 5 minutes and the plasma separated. Fasting plasma glucose (FBS) was determined by glucose oxidase method,, total cholesterol, LDL, HDL and, Triglyceride were determined by enzymatic methods. Hormone sensitive lipase was determined by, using dilaural-glycero-glutaric acid methyresoruffin as substrate and Cobas Integra 800 Auto-analyser. Growth Hormone was determined by Enzyme linked immunoassay method by using monoclonal antibodies and Access 2 Immunoassay system. All reagents were supplied by Roche Company.RESULT:The results showedpositive correlations between GH vs age and GH vs BMI. On the contrary, negative correlations were shown between GH vs the fasting levels of glucose,GH vs lipid and GH vs HSL.CONCLUSION:). GH caused the reduction of the blood levels of glucose and, lipid using HSL as mediator, by inhibiting gluconeogenesis and stimulating lipolysis, respectively