An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3′-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients

The availability of whole genome sequences in public databases permits genome-wide comparative studies of various bacterial species. Whole genome sequence-single nucleotide polymorphisms (WGS-SNP) analysis has been used in recent studies and allows the discrimination of various Brucella species and strains. In the present study, 13 Brucella spp. strains from cattle of various locations in provinces of South Africa were typed and discriminated. WGS-SNP analysis indicated a maximum pairwise distance ranging from 4 to 77 single nucleotide polymorphisms (SNPs) between the South African Brucella abortus virulent field strains. Moreover, it was shown that the South African B. abortus strains grouped closely to B. abortus strains from Mozambique and Zimbabwe, as well as other Eurasian countries, such as Portugal and India. WGS-SNP analysis of South African B. abortus strains demonstrated that the same genotype circulated in one farm (Farm 1), whereas another farm (Farm 2) in the same province had two different genotypes. This indicated that brucellosis in South Africa spreads within the herd on some farms, whereas the introduction of infected animals is the mode of transmission on other farms. Three B. abortus vaccine S19 strains isolated from tissue and aborted material were identical, even though they originated from different herds and regions of South Africa. This might be due to the incorrect vaccination of animals older than the recommended age of 4–8 months or might be a problem associated with vaccine production.

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Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v22i1.1206 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Eric H. Decloedt ◽

Phumla Z. Sinxadi ◽

Lubbe Wiesner ◽

John A. Joska ◽

David W. Haas ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

South African ◽

Genetic Polymorphisms ◽

Geometric Mean ◽

Hiv Positive ◽

P Value ◽

Nucleotide Polymorphisms ◽

Linear Regression Models ◽

Single Nucleotide ◽

Black South African

Background: Blood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacokinetics of their central nervous system (CNS) penetration.Objectives: We investigated genetic polymorphisms associated with CSF disposition of tenofovir and emtricitabine.Method: We collected paired plasma and CSF samples from 47 HIV-positive black South African adults who were virologically suppressed on efavirenz, tenofovir and emtricitabine. We considered 1846 single-nucleotide polymorphisms from seven relevant transporter genes (ABCC5, ABCG2, ABCB1, SLCO2B1, SCLO1A2, SLCO1B1 and ABCC4) and 782 met a linkage disequilibrium (LD)-pruning threshold.Results: The geometric mean (95% confidence interval [CI]) values for tenofovir and emtricitabine CSF-to-plasma concentration ratios were 0.023 (0.021–0.026) and 0.528 (0.460–0.605), respectively. In linear regression models, the lowest p-value for association with the tenofovir CSF-to-plasma ratio was ABCB1 rs1989830 (p = 1.2 × 10−3) and for emtricitabine, it was ABCC5 rs11921035 (p = 1.4 × 10−3). None withstood correction for multiple testing.Conclusion: No genetic polymorphisms were associated with plasma, CSF concentrations or CSF-to-plasma ratios for either tenofovir or emtricitabine.

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Genome-wide identification of breed-informative single-nucleotide polymorphisms in three South African indigenous cattle breeds

South African Journal of Animal Science ◽

10.4314/sajas.v46i3.10 ◽

1970 ◽

Vol 46 (3) ◽

pp. 302-312

Author(s):

A.A. Zwane ◽

A. Maiwashe ◽

M.L. Makgahlela ◽

A. Choudhury ◽

J.F. Taylor ◽

...

Keyword(s):

Principal Component Analysis ◽

Single Nucleotide Polymorphisms ◽

South African ◽

Principal Component ◽

Nucleotide Polymorphisms ◽

Indigenous Cattle ◽

Single Nucleotide ◽

Cattle Breeds ◽

Polymorphic Snps ◽

Genome Wide

Access to genotyping assays enables the identification of informative markers that discriminate between cattle breeds. Identification of these markers can assist in breed assignment, improvement and conservation. The objective of this study was to identify breed informative markers to discriminate between three South African indigenous cattle breeds. Data from BovineSNP50 and GeneSeek Genomic Profiler (GGP-80K) assays were generated for Afrikaner, Drakensberger and Nguni, and were analysed for their genetic differentiation. Hereford and Angus were included as outgroups. Breeds were differentiated using principal component analysis (PCA). Single-nucleotide polymorphisms (SNPs) within the breeds were determined when minor allele frequency (MAF) was ≥ 0.05. Breed-specific SNPs were identified using Reynolds Fst and extended Lewontin and Krakauer's (FLK) statistics. These SNPs were validated using three African breeds, namely N’Dama, Kuri and Zebu from Madagascar. PCA discriminated among the breeds. A larger number of polymorphic SNPs was detected in Drakensberger (73%) than in Afrikaner (56%) and Nguni (65%). No substantial numbers of informative SNPs (Fst ≥ 0.6) were identified among indigenous breeds. Eleven SNPs were validated as discriminating the indigenous breeds from other African breeds. This is because the SNPs on BovineSNP50 and GGP-80K assays were ascertained as being common in European taurine breeds. Lower MAF and SNP informativeness observed in this study limits the application of these assays in breed assignment, and could have other implications for genome-wide studies in South African indigenous breeds. Sequencing should therefore be considered to discover new SNPs that are common among indigenous South African breeds and also SNPs that discriminate among these indigenous breeds.

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Erratum: Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African Children

Journal of Medical Virology ◽

10.1002/jmv.23255 ◽

2012 ◽

Vol 84 (4) ◽

pp. 711-711

Author(s):

T.L. Kresfelder ◽

R. Janssen ◽

L. Bont ◽

M. Venter

Keyword(s):

Respiratory Syncytial Virus ◽

Single Nucleotide Polymorphisms ◽

South African ◽

Nucleotide Polymorphisms ◽

Vdr Gene ◽

Single Nucleotide ◽

Related Disease ◽

African Children ◽

Syncytial Virus ◽

South African Children

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Cross-sectional study of the association of 5 single nucleotide polymorphisms with enalapril treatment response among South African adults with hypertension

Medicine ◽

10.1097/md.0000000000027836 ◽

2021 ◽

Vol 100 (46) ◽

pp. e27836

Author(s):

Charity Masilela ◽

Brendon Pearce ◽

Joven Jebio Ongole ◽

Oladele Vincent Adeniyi ◽

Rabia Johnson ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Treatment Response ◽

South African ◽

Cross Sectional Study ◽

Nucleotide Polymorphisms ◽

Sectional Study ◽

Cross Sectional ◽

Single Nucleotide ◽

Enalapril Treatment

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Genomic Association of Single Nucleotide Polymorphisms with Blood Pressure Response to Hydrochlorothiazide among South African Adults with Hypertension

Journal of Personalized Medicine ◽

10.3390/jpm10040267 ◽

2020 ◽

Vol 10 (4) ◽

pp. 267

Author(s):

Charity Masilela ◽

Brendon Pearce ◽

Joven Jebio Ongole ◽

Oladele Vincent Adeniyi ◽

Mongi Benjeddou

Keyword(s):

Blood Pressure ◽

Single Nucleotide Polymorphisms ◽

South African ◽

Blood Pressure Response ◽

Pressure Response ◽

Response To Treatment ◽

Uncontrolled Hypertension ◽

Multivariate Logistic Regression Model ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

This study described single nucleotide polymorphisms (SNPs) in hydrochlorothiazide-associated genes and further assessed their correlation with blood pressure control among South African adults living with hypertension. A total of 291 participants belonging to the Nguni tribes of South Africa on treatment for hypertension were recruited. Nineteen SNPs in hydrochlorothiazide pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as blood pressure ≥140/90 mmHg. The association between genotypes, alleles and blood pressure response to treatment was determined by conducting multivariate logistic regression model analysis. The majority of the study participants were female (73.19%), Xhosa (54.98%) and had blood pressure ≥140/90 mmHg (68.73%). Seventeen SNPs were observed among the Xhosa tribe, and two (rs2070744 and rs7297610) were detected among Swati and Zulu participants. Furthermore, alleles T of rs2107614 (AOR = 6.69; 95%CI 1.42–31.55; p = 0.016) and C of rs2776546 (AOR = 3.78; 95%CI 1.04–13.74; p = 0.043) were independently associated with uncontrolled hypertension, whilst rs2070744 TC (AOR = 38.76; 95%CI 5.54–270.76; p = 0.00023), CC (AOR = 10.44; 95%CI 2.16–50.29; p = 0.003) and allele T of rs7297610 (AOR = 1.86; 95%CI 1.09–3.14; p = 0.023) were significantly associated with uncontrolled hypertension among Zulu and Swati participants. We confirmed the presence of SNPs associated with hydrochlorothiazide, some of which were significantly associated with uncontrolled hypertension in the study sample. Findings open doors for further studies on personalized therapy for hypertension in the country.

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