Association of genetic variants and the susceptibility to abnormal involuntary movements and tardive dyskinesia (TD) in Xhosa schizophrenia patients
Date
2007-03
Authors
Hitzeroth, Angelika
Journal Title
Journal ISSN
Volume Title
Publisher
Stellenbosch : University of Stellenbosch
Abstract
No obvious explanations exist for the development of abnormal involuntary movements (AIM), but
several hypotheses have been proposed for tardive dyskinesia (TD) development. Since TD seems
to have a genetic basis, several genetic variants have been investigated in TD development in
various populations. Few studies have focused on African populations. This study focused on
genetic variants (previously investigated in other populations) and the development and severity of
AIM and TD in a Xhosa schizophrenia population. Genotype and allele frequencies determined
were compared to those described in the literature for other populations. Following a report of an
association between Ala-9Val and schizophrenia in a Turkish population, this study subsequently
investigated this association in the Xhosa population.
MnSOD Ala-9Val was genotyped using HEX-SSCP analysis and the DRD3 Ser9Gly variant was
genotyped using restriction enzyme digestion by MscI. Genotyping was followed by statistical
comparisons of the various groups, as well as association analyses between the variant and
schizophrenia (only for MnSOD), AIM, or TD development and severity. The groups included a
Xhosa schizophrenia group, a subgroup of the Xhosa schizophrenia group that had AIM (AIM+)
and did not have AIM (AIM-), a subgroup of the AIM+ group that had TD (TD+), and a healthy
Xhosa control group. A possible interaction between Ala-9Val and Ser9Gly in the development of
AIM and TD was also investigated. Lastly, it was attempted to genotype CYP2D6*4, CYP2D6*10
and CYP2D6*17 using various PCR methods followed by restriction enzyme analysis.
MnSOD Ala-9Val genotype and allele frequencies were similar to those of the Turkish population,
but differed to those of the Asian populations. No association between Ala-9Val and the
development and severity of schizophrenia was found. However, a relationship between genotype
and AIM or TD development was observed, as well as an association between TD severity and Ala-
9Val genotype. DRD3 Ser9Gly genotype and allele frequencies were similar to those of the African
American population, but differed from other populations. No significant association between
Ser9Gly and the development and severity of AIM or TD was detected, nor was an interactive
effect between Ala-9Val and Ser9Gly in AIM or TD development observed. The genotyping of
CYP2D6 proved difficult and these variants could therefore not be analysed. The CYP2D6*4
genotype and allele frequencies that could be determined from some samples, were similar to the
frequencies described previously for African populations.
While we did not find an association between Ser9Gly in TD or AIM development and severity, nor
an interaction between Ala-9Val and Ser9Gly, we did observe a relationship between Ala-9Val and AIM or TD development and TD severity. The effect of this variant is probably small and other
variants, specifically those in genes involved in free radical removal should be investigated in
combination with Ala-9Val. With regard to CYP2D6 it is suggested that high-throughput
genotyping methods (e.g. microarray technology) should be used in the future. This will enable
simultaneous genotyping of several variants and can be used in various populations.
This study is the first of its kind by focusing on the unique South African Xhosa population and TD
or AIM development.
Description
Thesis (MSc (Genetics))—University of Stellenbosch, 2007.
Keywords
Schizophrenia -- South Africa -- Genetic aspects, Xhosa (African people) -- Health and hygiene, Tardive dyskinesia -- South Africa, Movement disorders -- South Africa, Genetic polymorphisms, Dissertations -- Genetics, Theses -- Genetics