ABCG2 polymorphisms and susceptibility to ARV-associated hepatotoxicity.

BACKGROUND: The ABCG2 421C/A polymorphism contributes significantly to the distribution and absorption of antiretroviral (ARV) regimens and is associated with the undesirable side effects of efavirenz. METHODS: To investigate this, we examined ABCG2 34G/A (rs2231137) and 421C/A (rs2231142) genetic variations in 149 HIV-infected patients (116 without hepatotoxicity, 33 with ARV-induced hepatotoxicity) and 151 healthy controls through the PCR-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS AND DISCUSSION: The ABCG2 34GA genotype and 34A allele indicated a risk for antiretroviral therapy-associated hepatotoxicity development (p = 0.09, OR = 1.58, 95% CI: 0.93-2.69; p = 0.06, OR = 1.50, 95% CI: 0.98-2.30). The haplotype GA was associated with hepatotoxicity (p = 0.042, OR = 2.37, 95% CI: 1.04-5.43; p = 0.042, OR = 2.49, 95% CI: 1.04-5.96). Moreover, when comparing HIV patients with hepatotoxicity to healthy controls, the haplotype GA had an association with an elevated risk for the development of hepatotoxicity (p = 0.041, OR = 1.73, 95% CI: 1.02-2.93). Additionally, the association of the ABCG2 34GA genotype with the progression of HIV (p = 0.02, OR = 1.97, 95% CI: 1.07-3.63) indicated a risk for advanced HIV infection. Furthermore, the ABCG2 421AA genotype was linked to tobacco users and featured as a risk factor for the progression of HIV disease (p = 0.03, OR = 11.07, 95% CI: 1.09-270.89). CONCLUSION: The haplotype GA may enhance the risk of hepatotoxicity development and its severity. Individuals with the ABCG2 34A allele may also be at risk for the development of hepatotoxicity. Additionally, individuals with an advanced stage of HIV and the ABCG2 34GA genotype may be at risk for disease progression.

Impact of inflammatory cytokine and adipokine gene variations in the development of HIV-associated lipodystrophy.

Cytokines affect lipid and glucose metabolism and also alter the body's habitus. They play a role in the development of lipodystrophy syndrome. Adipocytes secrete the pro-inflammatory cytokines IL-1, TNF-α and IL-6. The plasma cytokine concentration is associated with the percentage and distribution of fat tissue in the body. The metabolic disturbances are strongly associated with increased levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α). Plasma levels of cytokines such as TNF-α, IL-6 and leptin were found to be increased while plasma resistin levels were found to be variable in patients suffering from obesity and type II diabetes mellitus. Until now, limited information has been available on the polymorphism of cytokine and adipokine genes in patients of HIV-associated lipodystrophy (HIVLD), which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. Hence, we studied the association of cytokine and adipokine gene polymorphisms in various diseases and their impact on HIVLD. We carry out an extensive search using several databases, including PubMed, EMBASE and Google Scholar. The distribution of cytokine and adipokine gene polymorphisms and their expression levels varied among various populations. We examined the variants of cytokine and adipokine genes, which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. In the current review, we present a brief account of the risk factors of HIVLD, the pathogenesis of HIVLD and the polymorphism of cytokine and adipokine genes in various diseases with special reference to their impact on HIVLD.

APOBEC3, TRIM5α, and BST2 polymorphisms in healthy individuals of various populations with special references to its impact on HIV transmission.

AIDS restriction genes (ARGs) like APOBEC3, TRIM5α, and BST2 can act as immunological detectors of the innate protective mechanism of the body. ARGs influence the course of viral pathogenesis and progression of the disease. The infection caused by different viruses including HIV activates the innate immune receptors leading to production of proinflammatory cytokines, interferons and signals that recruit and activate cells involved in the process of inflammation following induction of adaptive immunity. Differential expression of genes involved in viral infection decide the fate and subsequent susceptibility to infection and its clinical outcome. Nevertheless, comprehensive reports on the incidence of genetic polymorphism of APOBEC3s, TRIM5α, and BST-2 in the general population and its association with pathological conditions have not been described well. Therefore, the occurrence of APOBEC3, TRIM5α, and BST2 polymorphism in healthy individuals and its impact on HIV transmission was analyzed. We conducted an extensive search using the several databases including, EMBASE, PubMed (Medline), and Google Scholar. APOBEC3-D, -F, -G, and -H out of the seven human APOBEC3s, help in the control of viral infection. Amongst various restriction factors, TRIM5α and BST-2 also restrict the viral infection followed by the development of the disease. In the current review, a brief account of the polymorphism in the APOBEC3G, TRIM5α, and BST2 genes are explored among different populations along with the interaction of APOBEC3G with Vif protein. Furthermore, this review specifically focus on ARGs polymorphism (APOBEC3G, TRIM5α, and BST2) associated with HIV transmission.

ACE2 and TMPRSS2 polymorphisms in various diseases with special reference to its impact on COVID-19 disease.

BACKGROUND: A carboxypeptidase protein called ACE2 is found in many organs. ACE2 protein can play a pivotal role to regulate the pathological changes of several diseases including COVID-19. TMPRSS2 gene is expressed in many human tissues and plays a critical role in spreading the infection of the viruses including coronavirus and progression of prostate cancer, and hence could be used as a potential drug target. There are limited reports on occurrence of genetic polymorphism of ACE2 and TMPRSS2 in general population, expressions in pathological conditions, and its impact on COVID-19 disease. Hence we comprehended the occurrence of ACE2, TMPRSS2 polymorphism in general population, expression in various diseases and its impact on COVID-19 disease. METHOD: We utilized multiple databases, PubMed (Medline), EMBASE and Google Scholar for literature search. DESCRIPTION: ACE2 polymorphisms have significant linkages with various diseases, including severity of SARS-CoV-2 infection. Genetic variations of these genes contribute to individual's genetic susceptibility to viral infection and its subsequent clearance. The diversity and variations in the population distribution of these genes, might greatly influence and in turn reflect into the observed population and gender differences of the severity and clinical outcomes of SARS-CoV-2 infection. CONCLUSION: There are diversities in distribution of ACE2 and TMPRSS2 polymorphisms among different populations. Analyzing the genetic variants and expression of ACE2 and TMPRSS2 genes, in a population may provide the genetic marker for susceptibility or resistance against the coronavirus infection, which might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.

COVID 19 pandemic: Mental health challenges of internal migrant workers of India.

COVID- 19, a biomedical disease has serious physical and tremendous mental health implications as the rapidly spreading pandemic. One of the most vulnerable, but neglected, an occupational community of internal migrant workers is prone for development of psychological ill-effects due to double whammy impact of COVID-19 crisis and concomitant adverse occupational scenario. Permutations and combinations of the factors viz susceptibility for new viral infections, potential to act as vectors of transmission of infection, high prevalence of pre-existing physical health morbidities such as occupational pneumoconiosis, tuberculosis, HIV infections, pre-existing psychological morbidities, adverse psychosocial factors like absence of family support and caretaker during the crisis, their limitations to follow the rules and regulations of personal safety during the COVID 19 crisis, social exclusion, and inability to timely access the psychiatric services; all give rise to the peri-traumatic psychological distress to internal migrant workers. Superadded, is the blow of financial constraints due to loss of work, absence or suspension of occupational safety and health-related basic laws with associated occupational hazards, which make this occupational group highly vulnerable for the development of psychological illnesses. We attempt to draw the attention of mental health professionals, general medical practitioners and occupational health policymakers to the various, interrelated and interdependent predisposing and causative factors for the development of psychological ill-effects amongst internal migrant workers with the interventions needed to address it, from an occupational health perspective angle.

Prevalence of ABCC3-1767G/A polymorphism among patients with antiretroviral-associated hepatotoxicity.

BACKGROUND: Plasma concentrations of antiretrovirals (ARVs) regimens have considerably varied in individuals of human immunodeficiency virus (HIV) because of variations in the expression of drug-metabolizing and transporter genes. Transporter genes play an important role in the disposition of drugs. Polymorphism in transporter gene (ABCC3) affects the MRP3 expression and varies the treatment outcome. METHOD: We examined the polymorphism of ABCC3-1767G/A gene in a total of 165 HIV patients (out of 165 HIV patients, 34 were with and 131 were without hepatotoxicity) and 156 healthy individuals using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: In univariate analysis, we found a decreased prevalence of ABCC3 1767GA, 1767GA+AA genotypes, and 1767A allele in patients with hepatotoxicity as compared to patients without hepatotoxicity (23.5% vs. 28.2% and 23.5% vs. 30.53%; 11.76% vs. 16.41%), while a higher prevalence of 1767AA genotype was observed in HIV patients in comparison with healthy controls (2.3% vs. 1.3%, odds ratio [OR] = 1.71, 95% confidence interval [CI]: 0.23-15.03, p = .89). The frequency of ABCC3-1767AA genotype was dispersed higher in individuals with early and advanced HIV disease stage in comparison with healthy controls (5.3% vs. 1.3%, OR = 4.73, p = .70; 8.9% vs. 1.3%, OR = 1.89, p = .91). A higher occurrence of ABCC3-1767AA genotype was found in tobacco using HIV patients without hepatotoxicity compared with nonusers (4.7% vs. 1.1%, OR = 4.28, p = .52). The distribution of ABCC3-1767GA genotype was higher in nevirapine receiving HIV patients irrespective of their hepatotoxicity status as compared to nonusers (30.4% vs. 9.1%, OR = 3.34, p = .22; 29.4% vs. 16.7%, OR = 1.69, p = .77). In multivariate analysis, HIV patients receiving nevirapine and with hepatotoxicity was found to have a significant risk for severity of hepatotoxicity (OR = 4.56, 95% CI: 1.60-12.99, p = .004). CONCLUSION: ABCC3 1767G/A polymorphism was not significantly associated with susceptibility to ARV-associated hepatotoxicity, although ABCC3 1767AA genotype designated a risk for acquisition of hepatotoxicity and advancement of the disease. Nevirapine usage emerged as an independent risk factor for hepatotoxicity severity.

Assessment of air pollution caused by illegal e-waste burning to evaluate the human health risk.

The onset of the 21st century has started a corresponding change in consumer lifestyles, resulting in the generation of a huge amount of the end-of-life electronics, known as e-waste. The e-waste recycling activities can pose a high risk to the environment and human health. We monitored air pollution levels (PM10) and heavy metal concentrations (Pb, Cu, Zn, Ni and Cr) in the air for three consecutive months in an area where illegal e-waste recycling was in operation and compared the results with other two residential sites. In addition, we measured the concentrations of the same heavy metals in human blood to find out if there exists any correlation between environmental and biological exposure. Hypoxemia and hypertension were also determined for the comparison of health status amongst the study population. The study design comprised of three sites, which were selected on the basis of different major activities in the respective areas. Air samples were collected with the help of RDS and subjected to heavy metals analysis by ICP-OES, whereas blood samples were analyzed by ICP-MS. Results showed that amongst all study sites significant highest mean concentration of PM10 (243.310 ±â€¯22.729 µg/m3) and its heavy metal was found at e-waste burning site (SIII). High levels of heavy metal in the air were responsible for the higher exposure to the residents of SIII. Therefore, the study concluded that e-waste burning by the informal sector has significantly contributed to the high levels of the air pollution, which in turn was responsible for the highest level of heavy metal exposure to the residents. This was also associated with the occurrence of cardiovascular morbidity namely hypertension amongst the inhabitants of SIII may indicate the effect of chronic exposure to the air pollution due to e-waste processing activities, which needs to be studied further.

Study of lead exposure to children residing near a lead-zinc mine.

This lead exposure study was conducted in a total of 452 school children in the age group of 9-14 years. Two hundred and ninety-eight exposed children came from the villages situated within a 2.5 km radius of the lead-zinc mine whereas the comparative group children were selected from the villages at least 10 km away from mine. Environmental monitoring study suggested that lead levels in air and water samples near the mining areas were within the Central Pollution Control Board prescribed standards. Lead levels in about 80% of the children were less than 10 µg/dl. Medical examination of all children did not show any signs related to lead toxicity but central nervous system-related symptoms, as reported by the subjects during medical examination, were found to be higher in the exposed group when compared with the comparative group. The values of physical growth parameters of the exposed group were comparable with that of the comparative group for both girls and boys. Hence, the physical growth of children was found to be unaffected by the observed level of lead exposure. To safeguard the health of the children residing near the mining area, various preventive and control measures were suggested.