Browsing by Author "Niehaus, Dana"
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- ItemCharacterization of the genetic variation present in CYP3A4 in three South African populations(Frontiers, 2013-02) Drogemoller, Britt; Plummer, Marieth; Korkie, Lundi; Agenbag, Gloudi; Dunaiski, Anke; Niehaus, Dana; Koen, Liezl; Gebhardt, Stefan; Schneider, Nicol; Olckers, Antonel; Wright, Galen; Warnich, LouiseThe CYP3A4 enzyme is the most abundant human cytochrome P450 (CYP) and is regarded as the most important enzyme involved in drug metabolism. Inter-individual and inter-population variability in gene expression and enzyme activity are thought to be influenced, in part, by genetic variation. Although Southern African individuals have been shown to exhibit the highest levels of genetic diversity, they have been under-represented in pharmacogenetic research to date. Therefore, the aim of this study was to identify genetic variation within CYP3A4 in three South African population groups comprising of 29 Khoisan, 65 Xhosa and 65 Mixed Ancestry (MA) individuals. To identify known and novel CYP3A4 variants,15 individuals were randomly selected from each of the population groups for bi-directional Sanger sequencing of∼600 bp of the 5'-upstream region and all thirteen exons including flanking intronic regions. Genetic variants detected were genotyped in the rest of the cohort. In total, 24 SNPs were detected, including CYP3A4∗12, CYP3A4∗15, and the reportedly functional CYP3A4∗1B promoter polymorphism, as well as two novel non-synonymous variants. These putatively functional variants, p.R162W and p.Q200H, were present in two of the three populations and all three populations, respectively, and in silico analysis predicted that the former would damage the protein product. Furthermore, the three populations were shown to exhibit distinct genetic profiles. These results confirm that South African populations show unique patterns of variation in the genes encoding xenobiotic metabolizing enzymes. This research suggests that population-specific genetic profiles for CYP3A4 and other drug metabolizing genes would be essential to make full use of pharmacogenetics in Southern Africa. Further investigation is needed to determine if the identified genetic variants influence CYP3A4 metabolism phenotype in these populations.
- ItemDigit ratio as an endophenotype in a schizophrenia population(AOSIS, 2021-03) Nieuwoudt, Wilhelm D. B.; Smit, Inge M.; Niehaus, Dana; Koen, Liezl; Jordaan, EsmeBackground: Schizophrenia is a debilitating mental health condition affecting the lives of many South Africans. The origins of the heterogeneity in the presentation of the illness remain uncertain. Aim: This cross-sectional study performed a retrospective data analysis to determine the usefulness of digit ratio as an endophenotype in a South African schizophrenia population. Setting: A large genetic study in a South African schizophrenia population recruited patients from services in the Western and Eastern Cape. Methods: Complete clinical histories were captured for participants, including sets of images of the face and extremities. Software was utilised to measure the lengths of participants’ digits from said images and digit ratios (2D:4D) were calculated. Descriptive analyses were performed on the ratios and statistical differences in digit ratio means were calculated between groups characterised by sex, age of onset and the presence vs absence of positive symptoms. Linear modelling was utilised to assess for correlates between 2D:4D and positive and negative symptom severity using scores obtained from the Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS). Results: 2D:4D in male participants did not significantly differ from female participants as in healthy populations. 2D:4D did not significantly correlate with the severity of positive or negative symptoms and 2D:4D means between groups did not significantly relate to age of onset. Conclusion: 2D:4D appears to be a possible endophenotype in schizophrenia in this population. 2D:4D, however, may not be as readily identifiable as certain minor physical anomalies and neurological soft signs significantly associated with schizophrenia in this population.
- ItemMothers’ pupillary responses to infant facial expressions(BioMed Central, 2017-02-06) Yrttiaho, Santeri; Niehaus, Dana; Thomas, Eileen; Leppanen, Jukka M.ENGLISH SUMMARY : Background: Human parental care relies heavily on the ability to monitor and respond to a child’s affective states. The current study examined pupil diameter as a potential physiological index of mothers’ affective response to infant facial expressions. Methods: Pupillary time-series were measured from 86 mothers of young infants in response to an array of photographic infant faces falling into four emotive categories based on valence (positive vs. negative) and arousal (mild vs. strong). Results: Pupil dilation was highly sensitive to the valence of facial expressions, being larger for negative vs. positive facial expressions. A separate control experiment with luminance-matched non-face stimuli indicated that the valence effect was specific to facial expressions and cannot be explained by luminance confounds. Pupil response was not sensitive to the arousal level of facial expressions. Conclusions: The results show the feasibility of using pupil diameter as a marker of mothers’ affective responses to ecologically valid infant stimuli and point to a particularly prompt maternal response to infant distress cues.
- ItemUse of traditional treatment methods in a Xhosa schizophrenia population(Health & Medical Publishing Group, 2003) Koen, Liezl; Niehaus, Dana; Muller, Jacqueline; Laurent, ClaudineENGLISH SUMMARY : No abstract available.