1,721,042 research outputs found
Pharmacogenetics of resistant hypertension: evaluating the role of genetic variation in ABCB1, ADBR1, CES1, CYP3A4, CYP3A5, NEDD4L, NOS3, NR3C2 and SCNN1B among South African hypertensive patient
Full text linkGlobally, it is estimated that over one billion individuals live with hypertension. The prevalence of resistant hypertension can be as high as 19% among African populations. Genetic variation in genes that affect the metabolism and transport of antihypertensive drugs has been reported to influence treatment outcome in patients with hypertension. However, there is substantial lack of data on which genetic variants are important in influencing how African patients with hypertension respond to treatment. We hypothesise that genetic variants previously reported to influence treatment outcome in hypertensive patients, may play a role in the development of resistant hypertension in Africans, as well as other novel variants. Therefore, this study set out to investigate the role of genetic variation in nine genes, namely, ABCB1, ADBR1, CES1, CYP3A4, CYP3A5, NEDD4L, NOS3, NR3C2 and SCNN1B, in the development of resistant hypertension in South African patients. Knowledge of pharmacogenetic variants that play a role in resistant hypertension may potentially improve treatment and management of hypertension in our populations. Materials and Method This was a retrospective matched case-control study. The study was conducted at the Hypertension Clinic at Groote Schuur Hospital, Cape Town, South Africa. The study was approved by the Human Research Ethics Committee (HREC) of the University of Cape Town (HREC 141/2022) and all patients had consented to be included in pharmacogenetic studies. Demographic and clinical variables were extracted from the patients' medical records. Patients with BP ≥ 140/90 mmHg on 3 or more antihypertensive drugs or BP 0.05) except for ABCB1 rs2032582 (P = 0.01), CES1 copy number (P 0.05). Discussion The CYP3A5 rs776746C allele is functionally associated with reduced CYP3A5 expression. This may lead to reduced clearance of antihypertensive drugs such as amlodipine, enalapril or spironolactone, increasing their exposure and efficacy. NOS3 rs3918188A allele may affect NOS3 gene expression, or its effect may be due to variants in linkage disequilibrium with it, leading to increased efficacy of antihypertensives drugs such as enalapril. ADRB1 rs1801252G allele or ADRB1 rs1801252A>G - rs1801253G>C, G-C haplotype alters ADRB1 receptor function, leading to reduced sensitivity to beta-blockers such as atenolol and consequently reduced efficacy. The NEDD4L rs4149601A allele results in a non-functional NEDD4L, impacting antihypertensive drugs with renal mechanisms, such as hydrochlorothiazide and amiloride. Conclusion CYP3A5 rs776746T>C, NOS3 rs3918188C>A, ADRB1 rs1801252A>G and NEDD4L rs4149601G>A may be variants of pharmacogenomics importance in Africans with respect to response to hypertension treatment. They seem to play a role in either predisposition to resistant hypertension or the pharmacogenomics of antihypertensive drugs. Pre-emptive screening for these variants may be of potential clinical utility in prescribing antihypertensive drugs by influencing decisions on suitable drug types or optimal drug doses in patients with hypertensio
APOE, PCSK9, and CETP genetic variants as potential biomarkers of dyslipidaemia in black South Africans with Type 2 Diabetes Mellitus
Full text linkDyslipidaemia is a commonly encountered clinical condition and is a major risk factor for cardiovascular diseases. Although there are many factors associated with dyslipidaemia, a strong genetic component is evident. Apolipoprotein E (APOE), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cholesteryl ester transfer protein (CETP) are key regulators of plasma cholesterol levels. Thus, genetic variation in the genes coding for these proteins contributes to dyslipidaemia. In this study, a cohort of black South African Type 2 Diabetes Mellitus (T2DM) patients was characterized for mutations in genes coding for APOE, PCSK9, and CETP, and the possible effects of these variants on their lipid profiles was evaluated. Participants (n=417) were recruited from the Chris Hani Baragwaneth Hospital Diabetes Clinic, Johannesburg from whom blood samples were obtained for DNA extraction. The cohort was further stratified into two groups; individuals on statin treatment (Sim+, n=291), and the second that was not on treatment (Sim-, n=87). Lipid profiles were determined by enzymatic methods. DNA was genotyped for APOE, PCSK9, and CETP variants using PCRRFLP and Sanger sequencing. Analysis of the effects of the genetic variants was carried out in two ways. Firstly, for all the participants combined, and then by separating those on statin treatment from those without (Sim+ vs. Sim-). Genotype and allele frequencies were calculated followed by genotype-phenotype correlations with lipid profiles. Univariate analysis showed a significant association between the APOE4 isoform and lower HDL-c levels in the combined cohort (p=0.034). The effects were more pronounced in the Sim- group (p=0.004) but were absent in the Sim+ group. Contrary to above, APOE2 was significantly associated with lower total cholesterol (TC) (p< 0.001) and lower LDL-c (p< 0.001) when compared to APOE3 in the combined cohort. Upon analysing treatment groups, the correlations were observed in the Sim+ group (p=0.027 and p=0.003, respectively), while there were no observed correlations in the Sim- group. The CETP rs34065661C/G and G/G genotypes were significantly associated with increased HDL-c levels (p=0.017; when applying a dominant genetic model) in the combined cohort, as well as in the Sim+ group (p=0.026). Multivariate analysis, using a generalized linear model, confirmed associations between APOE rs429358C and lower HDL-c (OR=0.881, p=1.64e04), and APOE rs7412T and decreased LDL-c (OR=0.759, p=0.012). No significant associations were observed for PCSK9 polymorphisms. We report significant associations between APOE and CETP genetic variations and altered lipid levels in this black South African T2DM population. These genetic variants could be biomarkers for dyslipidaemia among Africans. However, it is imperative that the APOE, PCSK9, and CETP genes are fully characterized for additional polymorphisms in order to come up with a better genetic profile that explains the variance in lipid levels observed in the black South African population. The impact of these genetic variants could be relevant to other black African populations as well
Pharmacogenetics of Efavirenz response in Bantu-speaking South African HIV/AIDS patients
No full textIncludes abstract.Includes bibliographical references (leaves 82-96).Efavirenz (EFV) is used in first-line antiretroviral (ARV) therapy of HIV-infected patients, and is principally metabolised by CYP1A2, CYP2A6, CYP2B6, CYP3A4/5 and the drug transporter ABCB1. Genetic variability in the above genes may contribute to differences in EFV plasma concentrations which affect the levels of viral suppression as well as development of side effects in patients. The aim of this project was to evaluate the effects of the different genetic polymorphisms on EFV plasma concentration levels in HIV/AIDS patients receiving first-line antiretroviral treatment (ART) containing EFV
Role of antiretroviral therapy exposure host genetics on cytomegalovirus infection status and association with gut microbiome profiles among pregnant black African women
Full text linkCytomegalovirus (CMV) is an important antenatal infection that is prevalent in the developing world. The disabling and potentially fatal effects of CMV acquisition or reactivation during pregnancy on the developing foetus and or neonate are known but, factors predisposing pregnant women to CMV are not well studied. CMV has a wide host cell tropism that includes gut epithelial cells. CMV infection in the gut epithelial cells results in a leaky gut and potential gut microbial dysbiosis. In this study, we set out to determine the prevalence of CMV infection as well as factors associated with CMV reactivation in a cohort of pregnant Zimbabwean women. We also aimed to determine the role of CMV infection and CMV susceptibility host genetics on gut bacterial profiles. Seroprevalence of CMV was determined using the enzyme-linked immunosorbent assay. A high prevalence of previous exposure to CMV, as denoted by the presence of anti-CMV IgG antibodies in participants' sera, was observed. Anti-CMV IgM antibodies that denote active CMV infection were detected in the sera of 4.6% (n=35/524) study participants. Prevalence of CMV was also determined using real time PCR, CMV reactivation was higher (6.7%) when using PCR than when using immunological assays (4.6%). The presence of CMV DNA was significantly associated with HIV positivity (p=0.04). PCR is the gold standard for CMV diagnosis, thus, CMV DNA positivity was used to denote CMV infection status in this thesis. The second objective was to determine if the differential effect of CMV acquisition or reactivation among HIV infected participants was due to variability in plasma efavirenz containing antiretroviral therapy (ART) exposure. Efavirenz (EFV) plasma concentrations were determined using high performance liquid chromatography (HPLC). Single nucleotide polymorphisms (SNPs) in the CYP2B6 gene, which encodes the main EFV metabolizing enzyme were genotyped. Carriers of CYP2B6 poor metaboliser (PM) genotypes (c.516T/T and c.983T/C) had significantly higher mean plasma EFV concentration compared to carriers of CYP2B6 fast metabolizer genotypes (i.e., c.516G/G and c.983T/T). CYP2B6 PM genotype carriers were significantly less likely to be positive for CMV DNA when compared with fast metabolizer genotype carriers (pC (p=0.002), TLR7 rs179008A>C (pC (p=0.003). In contrast, presence of the IL6 rs10499563T>C polymorphism was inversely correlated with CMV infection (p=0.002). The reported genetic variants are reported to modulate proteins involved in immune responses against viral infections, thus, their association with susceptibility to CMV infection. Such findings may assist in the designing of a muchneeded candidate CMV vaccine. Lastly, we set out to determine the possible role of CMV infection in shaping gut microbiota profiles. We report on a significant difference (p=0.001) in the beta diversity of gut bacterial profiles between HIV- and age-matched CMV-infected (cases) and CMVuninfected (controls) participants. Using linear discriminant analysis (LDA) effect size (LefSe), significant differences in the relative abundance of specific bacterial taxa were observed between cases and controls (p2). Significantly lower abundance of Lactobacillus reuteri and Roseburia, genera associated with lower microbial translocation was observed in cases than controls. Lower relative abundance of Lactobacillus and Roseburia, is consistent with microbial translocation and heightened inflammation, respectively, hence higher likelihood of microbial translocation and inflammation occurring in cases than controls. Furthermore, Prevotella copri, a species that has been association with cytokine release and chronic inflammation was significantly more abundant in cases than controls. CMV is a known chronic inflammatory condition, and this study provides further confirmation through the higher relative abundance of P.copri in cases than controls. Biomarker identification has proven to be a successful means of translating molecular data into clinical practice, such as vaccine development in the case of CMV infection. Overall, this study reports the possible interaction of various host factors in facilitating CMV acquisition or reactivation during pregnancy. In the setting of HIV-CMV coinfection, our findings emphasise on the need for genotype guided drug dosage to achieve therapeutic EFV so as to maintain the balance between host and coinfecting microbes in HIV management. Comprehensive genotype guided drug dosage, if taken as a once-off test should be affordable especially in resource-limited settings. This is particularly important in pregnant women who are at a risk of vertically transmitting infection to the immunologically immature foetus and or neonate. Data from this study may assist in curbing the host associated challenges in designing an effective CMV vaccine. Moreover, the biomarkers reported may assist in diagnosis and management of potential CMV acquisition or reactivation during pregnancy. However, bigger prospective, functional studies would be needed to confirm the exact roles of the biomarkers identified in this study in the diagnosis, prognosis and therapeutics of CMV infection
Type 2 diabetes mellitus and dyslipidaemia: effects of genetic variation in African populations
Full text linkBackground: Low-density lipoproteins (LDL) have been associated with damage to the
cardiovascular system in patients with type 2 diabetes mellitus (T2DM). These patients are
two (2X) to four (4X) times more likely to develop cardiovascular diseases (CVD) compared
to non-diabetic patients due to dysfunctional lipoprotein metabolism. Normal lipid
metabolism involves interconversion and transfer of molecules regulated by several enzymes
such as Apolipoprotein E (ApoE) and proprotein convertase subtilisin/kexin type 9 (PCSK9).
ApoE and PCSK9 are involved in clearance of lipoproteins and therefore, influence lipid
profiles. Association between ApoE and T2DM in cardiovascular diseases have been widely
reported. PCSK9 on the other hand is emerging as an important player in lipid metabolism
but its effects in diabetes are not known. Studies on both ApoE and PCSK9 in African
populations are in its infancy. Each year, CVD kills more people than any other cause of
death. Many CVDs can be traced back to pathological process of atherosclerosis, in which
fatty material collects along walls of arteries, limiting flexibility and obstructing blood flow.
T2DM alone has been classified as a major factor for development of CVD and one of its
complications is the development of dyslipidaemia. Unlike PCSK9, genetic polymorphisms
in ApoE have been well characterised as important dyslipidaemia genetic markers associated
with coronary artery disease. The association between ApoE and PCSK9 gene
polymorphisms with dyslipidaemia in T2DM was evaluated. Diabetic dyslipidaemia presents
as a triad of high triglycerides, high LDL and low high-density lipoprotein (HDL).
Aims and Objectives: This study aimed to evaluate the role of genetic variation in genes
coding for ApoE2 and PCSK9 on dyslipidaemia in South African diabetic patients. Main
objectives’ included recruitment of participants, genetic characterisation of ApoE and PCSK9
and determination of the lipid profiles for the recruited participants.
Methods: Two hundred and forty-four (n=244) participants were recruited from the
Baragwaneth diabetic clinic, using a retrospective approach. The participants comprised of
two groups, (i) dyslipidaemic, and (ii) non-dyslipidaemic (controls). The dyslipidaemic group
was further divided into three groups; i) those with high cholesterol only, ii) those with high
triglycerides only and iii) those with both high cholesterol and triglycerides which is referred
to as the mixed group. Clinical and demographic parameters were retrieved from hospital
records with the consent of the participants. Ethical clearance was obtained from the University of Cape Town and University of Witwatersrand. Genetic characterisation of ApoE
was carried out using polymerase chain reaction (PCR) coupled to restriction fragment length
polymorphism (RFLP) and confirmed through sequencing while characterisation for PCSK9
was carried out through Sanger sequencing.
Results: Of the 244 participants, 165 were dyslipidaemic while 79 were not dyslipidaemic.
The 165 dyslipidaemic participants were further divided into 33.3% (n=55) those with high
cholesterol, 29.1% (n=48) those with high triglycerides and 37.6% and (n= 62) those with
high cholesterol and triglycerides (mixed). The cohort comprised of 128 (52%) females,
median (IQR) age 56.0 (48.0 – 64.0) years and 116 (48%) males with median (IQR) age of
56.5 (48.0 – 63.0) years. Most of the characteristics between the dyslipidaemic and nondyslipidaemic participants were significantly different as expected in a purposive sampling
technique. ApoE3/4 genotype had the highest frequency distribution (41%) while ApoE2/3
genotype had the lowest frequency (7%). An uncharacterised ApoE referred to in the study as
ApoE X with a frequency distribution of 6%, was reported for the first time. The selected
measured parameters evaluated against a set of variables showed a significant association
between HbA1c and age (p=<0.008) is reported. TC (p=0.00092), LDL (p=0.0184) and TG
(p=0.0175) were strongly associated with poor glycaemic. Both LDL (p=0.0174 and HDL
(p=0.0072) were associated with age. Homozygous ApoE2/2 and heterozygous ApoE2/3
genotypes correlated with poor glycaemic control with a median HbA1c of 10.95% (IQR
5.88-14.98%) and 10.20% (IQR 6.20-15.80%), respectively; while homozygous ApoE4/4
carriers displayed good glycaemic control with a median HbA1c of 6.60% (IQR 5.70 –
2.30%). Carriers of homozygous ApoE3/3 genotype had the highest median TC of
6.06mmol/L (IQR 5.48 -– 6.71mmol/L) while homozygous ApoE4/4 carriers had the highest
median triglycerides of (2.94 (IQR 1.75 – 5.13 mmol/L). Carriers of homozygous PCSK9
rs505151 A/A (E670G) genotype had the highest frequency distribution in both groups of
participants with dyslipidaemic (55.1%) and non-dyslipidaemic (63. 5%), followed by
carriers of heterozygous PCSK9 rs505151G/A at 40.6% and lastly carriers of PCSK9
rs505151G/G at (9.5%). On the other hand, carriers of homozygous PCSK9 rs28362286 C/C
genotype were predominantly distributed with a frequency of 94.2% and
PCSK9rs28362286C/A had a very small frequency distribution of 5.8% while
PCSK9rs28362286A/A was absent in this population. Carriers of PCSK9 rs505151A/A
genotype had higher HbA1c with a median of 10.10% (IQR 7.48 – 12.90) compared to PCSK9 rs505151 G/A genotype with a median of 9.00% (IQR 7.03 –11.35). The results
show that PCSK9 rs505151G/A with lower HbA1c had non-significantly higher TC, LDL,
TG and non-HDL but lower HDL compared to PCSK9 rs505151A/A genotype. The results
revealed no direct reciprocal relationship between glycaemic control and level or type of
dyslipidaemia.
Conclusions: The study showed the effects of ApoE and PCSK9 genetic variation on the
dyslipidaemia seen in black South African diabetic participants. Therefore, this study through
ApoE and PCSK9 genotypes show that the diabetic dyslipidaemia has an underlying genetic
influence. In addition, to the well-characterised ApoE genotypes, an uncharacterised
genotype referred to as ApoE X genotype is reported. With these findings, consideration to
explore possible underlying genetic predisposition is recommended especially in diabetic
patients with dyslipidaemia that responds poorly to standard therapy
Virus restriction gene variants and their possible role in neurocognitive function in children born to HIV-infected mothers
No full textIncludes abstract.Includes bibliographical references.Host genetic variation is an important determinant of HIV infection, disease progression and HIV-associated neurocognitive deficits. However, there is no sufficient knowledge on the role of genetic variants especially among African populations. This study is focused on investigating variation in HIV/AIDS restriction genes; CCR2, CX3CR1, SDF1, RANTES, APOBEC3G and MBL2 and their possible role in HIV infection and neurocognitive function among children born to HIV infected mothers, recruited in Harare, Zimbabwe. A total of 116 children comprising of 73 perinatally exposed to HIV (34 who were born infected and 39 who were uninfected) and 43 unexposed controls were recruited in 2011(at ages 7-9 years) from a cohort of mother-baby pairs that has been followed up since 2002. The demographic characteristics of the recruited children were captured from their medical records. A McCarthy Scale of Children‟s Abilities (MSCA) was administered to determine each child‟s neurocognitive status. Genotyping for allelic variants was done using PCR-RFLP, SNaPshot® and Sanger DNA sequencing. Statistical analysis was carried out to determine association between genotypes, HIV status and neurocognitive function. The observation of different genetic variants or combinations of genotypes between the HIV-exposed and infected group and that of the HIV-exposed but uninfected group may be a pointer to critical pathways in differential HIV susceptibility. Exposure and infection with HIV is controlled by a multitude of genes/processes, thus, SNPs are unlikely to show statistically significant effects individually and may be more useful in a multifactorial model, as observed from comparisons of genotype combinations and haplotypes. The role of host genetic variation on neurocognitive function remains disputed but our observations suggest innate immune factors such as MBL2 may have a pronounced effect. Therefore, it may be possible to genotype for a suite of genes and use them as markers of either HIV susceptibility or neuro-developmental patterns
Genetic polymorphisms in the drug metabolizing genes and their roles in the development of oesophageal cancer
No full textIncludes bibliographical references (leaves 109-130).Although the incidence and mortality due to the oesophageal squamous cell carcinoma (OSCC) in Black South Africans is extremely high, very little is known about the aetiology and molecular biology of the disease. In order to make a contribution to the understanding to the causes of this disease we investigated the role of the polymorphisms in the genes coding for the cytochrome P450 (CYP1A1, CYP1A2, CYP1B1, CYP2E1), sulphotransferase 1A1 (SULT1A1), glutathione S-transferases (GSTT1. GSTM1 and GSTP1) alcohol dehydrogenase (ADH2 and ADH3) and aldehyde dehydrogenase (ALDH2) because the products of these genes are involved in the metabolism or biotransformation of harmful compounds
Determining the role of differential expression of candidate icroRNAs in cardiometabolic diseases among South African adults living with HIV
Full text linkBackground: MicroRNAs (miRNAs) are potential prognostic/diagnostic markers that have been investigated for screening of cardiometabolic disease (CMD) risk in general populations. However, little is known about their value in people living with human immunodeficiency virus (PLWH), who have an increased susceptibility to CMDs. PLWH have an increased susceptibility to CMDs because of chronic inflammation caused by a persistent immune response, metabolic complications from antiretroviral therapies, and traditional risk factors. In this study the association of differential expression of candidate miRNAs, miR-126-3p, -223-3p, and -320a with CMDs was investigated among PLWH. Methods: Using a cross-sectional study design ≥18-year-old PLWH were recruited from 17 random HIV clinics in the Western Cape, South Africa between 2014-2015. Standard international definitions were used to diagnose CMDs. Whole blood miRNAs were isolated, and expression quantified by reverse transcription quantitative polymerase chain reaction. MiRNA expression was compared between participants with a CMD and without for each investigated outcome, using Wilcoxon rank sum/Kruskal Wallis tests. Robust correlations, robust linear regressions and logistic regressions assessed miRNAs relationships with cardiometabolic risk profiles. A p-value <0.05 was considered statistically significant. Results: Among 675 participants (81% women), prevalence of CMDs/traits was: elevated highsensitivity C-reactive protein (67.4%), raised waist circumference (WC) (63.3%), obesity (34.1%), insulin resistance (IR) (9.9%), and diabetes mellitus (8.6%). Target miRNAs were not significantly differentially expressed based on individual CMD statuses. However, target miRNAs were significantly correlated with glucose homeostasis variables [fasting glucose (r≤0.129, p≤0.046); fasting insulin (r≤0.115, p≤0.015); 2-hour insulin (r≤0.097, p≤0.029); and homeostatic model assessment of insulin resistance (HOMA-IR) (r≤0.144, p≤0.002)], and miR126-3p and -223-3p were significantly correlated with alanine transaminase (r≤0.128, p≤0.022). In linear regression models after adjusted for age and gender, miR-126-3p had a borderline association with HOMA-IR (β≤0.018, p≤0.081), while miR-223-3p was borderline associated with glucose when adjusted for age, gender, and WC (β=0.001, p=0.066). There were no significant associations in logistic regression models. Conclusion: The miRNAs tested in this study appear not to be important markers for CMDs in PLWH. A genome-wide approach is recommended to uncover other miRNAs with potential as biomarkers of CMDs in PLWH
Distal sensory polyneuropathy in HIV/TB co-infection : the role of vitamin B6 and N-acetyltransferase 2 genetic variation
No full textBoth human immunodeficiency virus (HIV) infection and tuberculosis (TB) are complicated by a painful distal sensory polyneuropathy (DSP) that may be due to virus-related HIV-DSP, antiretroviral toxic neuropathy (ATN) or isoniazid-induced peripheral neuropathy (INH-PN). In co-infection with and co-treatment for HIV/TB, DSP risk is increased. Factors driving this risk may be vitamin B6 deficiency and slow metabolism of INH mediated by N-acetyltransferase 2 (NAT2) acetylation, both known ris
Human host and malaria parasite genome variations to susceptibility to malaria
No full textBackground: Inter-ethnic differences in response to medication can be explained through population structure as observed from genetic variants affecting drug metabolism. Antimalarial drugs are used in populations carrying different profiles of genetic variability. However, there is limited information on the distribution of genetic variants of pharmacogenomics importance in African populations. Aims: We set out to determine whether there are differences in the pharmacogenetic profiles when comparing populations residing in malaria endemic and non-endemic areas. Methodology: Genome-wide genotype datasets (n=13, 447) from four malaria endemic African populations, including Mali, Kenya, Gambia, and Malawi, which were part of the MalariaGEN consortium, were accessed. As comparator, reference datasets of global populations comprising of 20 ethnic groups (n~5,000) from African Genome Variation Project (AGVP) and 1000 Genome consortium project were accessed, considering their malaria epidemiology. Pharmacogenes that are verified from databases such as PharmVar and PharmGKB, and nomenclature sites for uridine 5'-diphospho-glucuronosyltransferases (UGT), solute carrier (SLC) transporters, ATP-binding cassette (ABC) transporters, thiopurine Smethyl transferase (TPMT), and N-acetyltransferases (NAT) were used. Pharmacogenes reported to affect antimalarial drugs were noted and their distribution analysed. Single nucleotide polymorphisms (SNPs) that map to pharmacogenes were retrieved from dbSNP databases and used in the comparison of the populations from malaria endemic and nonendemic regions, through population structure evaluation using pharmacogenes variants. As part of confirmation, genotyping for CYP2C8 SNPs was carried out in native South African population groups, which we have access to our laboratory. CYP2C8 is particularly interesting because of its central involvement in the metabolism of some of the major antimalarial drugs. Results: There were quantitative and qualitative differences in the distribution of pharmacogenes variants when comparing populations from malaria endemic regions to those from non-endemic regions. For instance, the analysis of the minor allele frequency (MAF) proportion of all pharmacogenes variants obtained from the databases revealed that a high proportion of common variants (MAF > 0.05) of pharmacogenes were higher in the four African population from malaria endemic areas (MAF proportion > 50%) compared with world populations from malaria non-endemic areas (MAF proportion 80%) compared to non-endemic populations ( 80%) in the malaria endemic populations. The ABC drug transporters such as ABCC4, ABCC1 and ABCC2 were found to have a higher proportion of pathogenic SNPs in populations of the four malaria endemic areas (> 50%) compared with those from non-endemic areas (A (*2), rs11572101A>G, rs11572100T>C and rs1926705C>T), characterized in South Africans, were found to have III statistically significant difference (p-value A (*2), was found in the South African population. This may also have relevance for future consideration of pharmacogenetic testing for a person traveling to malaria endemic areas from non-endemic areas, such as South Africa. Future studies should be done using large scale sequencing datasets from malaria endemic areas and assess the effect of common variants of antimalarial pharmacogenes on the safety and efficacy of currently used antimalarial drugs
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