Abstract:
Fetal alcohol spectrum disorder (FASD) encompasses a range of conditions induced by
prenatal alcohol exposure. Fetal alcohol syndrome (FAS) is the most severe of these
conditions. FAS is characterised by discriminating facial features along with growth
deficiencies and central nervous system abnormalities.
FASD is a growing concern in South Africa, particularly in the Northern and Western
Cape Provinces. In the Northern Cape, astounding prevalence rates of 122 and 73.8 per
1000 school entry children have been established for the towns of De Aar and Upington
respectively.
Studies involving twin concordance research and animal models have indicated that there
is a genetic influence contributing towards FAS susceptibility in individuals. FAS is
considered a complex disease whereby both genetic and environmental factors interact in
disease pathogenesis. For this reason a case-control study involving the investigation of
appropriate candidate genes was conducted.
The neuronal migration pathway in the developing brain is targeted by prenatal alcohol
exposure. The astrotactin (ASTN) and reelin (RELN) genes were selected for investigation
based on their fundamental role in neuronal migration. A FAS case-control study
involving 45 cases and 112 controls was conducted on the Northern Cape Coloured
population.
Four single nucleotide polymorphisms (SNPs) including missense and non-coding
variants were selected within ASTN and four missense SNPs were selected within RELN.
The study aimed to determine the genotype and allele frequencies of the variants within
the case and control groups and to assess whether any association between the gene
variants and the predisposition to FAS existed. Statistical analyses indicated a significant
genotypic association (P= 0.049) between RELN’s rs607755 marker; the C/T genotype
was more likely to be found amongst controls thus inferring a possible protective effect against FAS. A logistic regression model supported the above association by indicating
the C/T genotype as being independently significant (P= 0.026).
The most limiting factor of this study was the small sample size and consequent lack of
power to detect genes with minor effects. It would therefore be suggested that the study be
repeated once a larger sample size has been established. A larger sample size would
increase the chances of detecting true associations between genes of minor effect and
FAS, thus minimising false-positive associations from arising.
