Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4+ T cell counts in Ghanaian HIV patients

Kuleape, Joshua Agbemefa; Tagoe, Emmanuel Ayitey; Puplampu, Peter; Bonney, Evelyn Yayra; Quaye, Osbourne

doi:10.1371/journal.pone.0195954

Cited by 11 publications

(12 citation statements)

References 30 publications

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“…Therefore, identification of these genes in our antiretroviral-prescribed patients could facilitate the determination of higher-risk groups. The frequency of the double deletion found in our population 11.2% was lower than those reported in Ivory Coast 14.3% [24], Ghana 16.66% [26], Morocco 15.5% [27], Egypt 16.25% [28], Tunisia 18% [28] and Sudan 32.9% [29], but higher than that seen in Algeria 7.31% [30] and Namibia 3% [31]. The distribution of the mutant allele G in GSTP1 gene observed in our population 49.76% was statistically comparable to that reported in the Gambian population 53.6%, (p = 0.2).…”

Section: Discussioncontrasting

confidence: 76%

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population

et al. 2019

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Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

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Section: Discussioncontrasting

confidence: 76%

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population

et al. 2019

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“…Although the differences were not statistically significant, this shows that there is a possibility that the +510 CT SNP has an impact on the progression of the diseases by having an impact on the lymphocytes differentiation and maturation. A study conducted among HIV patients in Ghana, showed that changes particularly deletions on the glutathione S-transferases genes was associated with normal CD4 counts (Kuleape et al, 2018). Our results suggest that the IL-7 receptor gene at +510 polymorphism affects the level of CD4 count among HIV positive patients however there is no data on the association with the serum level of IL-7 receptor itself.…”

Section: Discussioncontrasting

confidence: 51%

Research Article Genetic polymorphism at Interleukin-7 receptor gene at +510 position and its impact on pain and other symptoms among HIV and AIDS patients

Nangammbi¹,

Moloro²,

Samie³

2019

Genet. Mol. Res.

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Genetic polymorphism of cytokine genes has been shown to be associated with susceptibility to diseases. We investigated the frequency of the IL-7 receptor-α +510 CT SNP in relation to pain and other symptoms among HIV and AIDS patients attended at various South African hospitals for treatment. Demographic as well as clinical data was obtained through structured interviews and patient files were consulted. A total of 107 mouth wash samples were obtained from volunteers, and DNA was extracted from these samples using the Qiagen protocol. Genotyping of the IL-7 receptor +510 CT SNP was conducted using sequence specific PCR. The CC and TC genotypes were the most common, while the TT genotype was rare (47.7, 45.8 and 6.5% respectively). The CC genotype was more common among patients who had body pain at the time they went for testing (χ 2 = 4.75; P = 0.029) while the TC genotype was more common among those that did not have pain (χ 2 = 6.86; P = 0.009). The TC genotype was also more common among patients who did not have genital sores (χ 2 = 4.663; P = 0.031). The TT genotype was more common among patients whose infection state had improved as well as among those who had tuberculosis, although the differences were not significant. We concluded that the CC genotype is associated with pain while the TC ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 18 (4): gmr18292 T.C. Nangammbi et al. 2 genotype is protective of pain and genital sores. Further studies will be needed to confirm these hypotheses in larger populations.

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“…Depletion of circulatory endogenous antioxidants, including reduced glutathione (GSH) and vitamins have also been observed in HIV-infected patients, and the lower antioxidant levels correlate with low CD4 + counts [9,10]. A recent study from our research group reported that homozygous deletion of GSTM1 and GSTT1 genes has no effect on total GST activity in the serum of HIV-infected individuals, and the observed enzyme activity was attributted to a compensatory mechanism due to other enzymes that play a role in metabolising xenobiotics [11]. Even though it was expected in the previous study that a double deletion of the GST polymorphic gene will result in a decrease in the total GST enzyme activity, and play a role in disease conditions such as cancers [12,13], the contrary finding suggests that antioxidant enzymes activities in HIV patients may be influenced by other factors such as race, geographical location and trace elements.…”

Section: Introductionmentioning

confidence: 99%

Imbalance of antioxidant enzymes activities and trace elements levels in Ghanaian HIV-infected patients

et al. 2019

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Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) have been associated with high oxidative stress in HIV patients. The disparity in antioxidant-oxidant levels in HIV patients favours viral replication and disease progression. This study aimed at determining the effect of ART on antioxidant enzymes activities and trace elements levels in Ghanaian HIV patients. A total of 242 participants; comprising of 105 HIV-infected patients on ART, 77 HIV-infected ART-naïve, and 60 HIV seronegative controls were recruited for the study. Whole blood was collected and used for haematological profiling, and the determination of CD4 + counts, superoxide dismutase (SOD) activity and trace element levels. Serum was used for liver function tests and the determination of glutathione reductase (GR) activity, and plasma was used to estimate reduced glutathione (GSH) levels. Low levels of haemoglobin (HB), hematocrit, mean cell volume (MCV) and mean cell hemoglobin (MCH), and trace elements were found in ART-naïve patients compared to those on ART and the seronegative controls. In the ART-naïve patients, glutathione reductase (GR) activity and reduced glutathione (GSH) level were significantly low compared to patients on ART and seronegative controls. Activity of SOD was significantly reduced in ART-naïve patients compared to those on ART and the control group, and manganese is the only trace element that showed a strong negative correlation with SOD activity and a positive and significant correlation with CD4 + count, and therefore needs to be investigated further. The study suggests that assessing antioxidant levels or enzymes activities of patients infected with HIV should be considered during therapy.

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Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4+ T cell counts in Ghanaian HIV patients

Cited by 11 publications

References 30 publications

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population

Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population

Research Article Genetic polymorphism at Interleukin-7 receptor gene at +510 position and its impact on pain and other symptoms among HIV and AIDS patients

Imbalance of antioxidant enzymes activities and trace elements levels in Ghanaian HIV-infected patients

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