No abstract

Fetal alcohol syndrome (FAS) is a devastating developmental disorder resulting from alcohol exposure during fetal development. It is a considerable public health problem worldwide and is characterized by central nervous system abnormalities, dysmorphic facial features, and growth retardation. Imprinted genes are known to play an important role in growth and development and therefore four imprinting control regions (ICRs), H19 ICR, IG-DMR, KvDMR1 and PEG3 DMR were examined. It is proposed that DNA methylation changes may contribute to developmental abnormalities seen in FAS and which persist into adulthood. The participants included FAS children and controls from the Western and Northern Cape Provinces. DNA samples extracted from blood and buccal cells were bisulfite modified, the ICRs were amplified by PCR and pyrosequencing was used to derive a quantitative estimate of methylation at selected CpG dinucleotides: H19 ICR (six CpG sites; 50 controls and 73 cases); KvDMR1 (7, 55, and 86); IG-DMR (10, 56, and 84); and PEG3 DMR (7, 50, and 79). The most profound effects of alcohol exposure are on neuronal development. In this study we report on epigenetic effects observed in blood which may not directly reflect tissue-specific alterations in the developing brain. After adjusting for age and sex (known confounders for DNA methylation), there was a significant difference at KvDMR1 and PEG3 DMR, but not the H19 ICR, with only a small effect (0.84% lower in cases; p = 0.035) at IG-DMR. The two maternally imprinted loci, KvDMR1 and PEG3 DMR, showed lower average locus-wide methylation in the FAS cases (1.49%; p < 0.001 and 7.09%; p < 0.001, respectively). The largest effect was at the PEG3 DMR though the functional impact is uncertain. This study supports the role of epigenetic modulation as a mechanism for the teratogenic effects of alcohol by altering the methylation profiles of imprinted loci in a locus-specific manner.

Aims: Genetic variation at the apolipoprotein E (apoE) locus is an important determinant of plasma lipids. The aim of the present study was to evaluate the association between apolipoprotein E genotype and plasma lipid levels among a rural black population in South Africa. Methods: Lipid levels and apoE genotypes were studied in 505 volunteer subjects (363 women, 142 men) resident in the Dikgale demographic surveillance site. Results: Allele frequencies were found to be 0.190 for e2, 0.518 for e3, and 0.293 for e4, indicating a relatively low frequency of the e3 allele and a high frequency of the e4 allele. To determine the effect of apoE polymorphism on lipid levels three groups were formed: namely e2-, e3-, and e4-expressing groups. A significant effect of the apoE genotype on total cholesterol, low-density lipoprotein cholesterol (LDL-C), highdensity lipoprotein cholesterol (HDL-C)/Total cholesterol (TC) ratio, and triglycerides was observed. LDL-C was significantly lower and the HDL-C/TC ratio was significantly higher in the e2 group compared with the e3 and e4 groups. Triglyceride levels were significantly higher in the e2 group than in the e3 group. Conclusions: With the unfavourable apoE allele distribution, and the lifestyle changes taking place in rural South African populations, preventive strategies need to be developed to limit a potential epidemic of cardiovascular disease in the black population of South Africa.