Prevalence of APOL1 Risk Variants in Afro-Descendant Patients with Chronic Kidney Disease in a Latin American Country.
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ABSTRACT:
Methods: This is an observational cross-sectional study. Afro-descendant patients with ESRD in waitlist or recipients of kidney transplant were evaluated. Clinical data were collected from the electronic medical records. Genotyping was carried out by amplification of the exon 7 of the APOL1 gene. For the identification of risk genotypes, the bioinformatics tool BLAST was used.
Results: We enrolled 102 participants. The frequency of APOL1 risk variants was 67.2%, in which 24.5% (n?=?25) were G1 heterozygous and 5.8% (n?=?6) were G2 heterozygous and 37% of the patients had high-risk status with two alleles in homozygous (G1/G1?=?21 and G2/G2?=?3) or compound heterozygote (G1/G2?=?14) form.
SUBMITTER: Duran CE
PROVIDER: S-EPMC6935820 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients. METHODS:In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. RESULTS:In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). CONCLUSIONS:Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
| S-EPMC3969022 | biostudies-literature
Project description:Recent studies have identified genetic variants in APOL1 that may contribute to the increased incidence of kidney disease in populations with African ancestry. Here, we review the biology of APOL1 present in the circulation and localized to the kidney as it may contribute to the pathogenesis of APOL1-associated kidney disease.
| S-EPMC4022720 | biostudies-literature
Project description:BackgroundClandestine induced abortions are a public health problem in many developing countries where access to abortion services is legally restricted. We estimated the prevalence and incidence of, and risk factors for, clandestine induced abortions in a Latin American country.MethodsWe conducted a large population-based survey of women aged 18-29 years in 20 cities in Peru. We asked questions about their history of spontaneous and induced abortions, using techniques to encourage disclosure.ResultsOf 8242 eligible women, 7992 (97.0%) agreed to participate. The prevalence of reported induced abortions was 11.6% (95% confidence interval [CI] 10.9%-12.4%) among the 7962 women who participated in the survey. It was 13.6% (95% CI 12.8%-14.5%) among the 6559 women who reported having been sexually active. The annual incidence of induced abortion was 3.1% (95% CI 2.9%-3.3%) among the women who had ever been sexually active. In the multivariable analysis, risk factors for induced abortion were higher age at the time of the survey (odds ratio [OR] 1.11, 95% CI 1.07-1.15), lower age at first sexual intercourse (OR 0.87, 95% CI 0.84-0.91), geographic region (highlands: OR 1.56, 95% CI 1.23-1.97; jungle: OR 1.81, 95% CI 1.41-2.31 [v. coastal region]), having children (OR 0.82, 95% CI 0.68-0.98), having more than 1 sexual partner in lifetime (2 partners: OR 1.61, 95% CI 1.23-2.09; > or = 3 partners: OR 2.79, 95% CI 2.12-3.67), and having 1 or more sexual partners in the year before the survey (1 partner: OR 1.36, 95% CI 1.01-1.72; > or = 2 partners: OR 1.54, 95% CI 1.14-2.02). Overall, 49.0% (95% CI 47.6%-50.3%) of the women who reported being currently sexually active were not using contraception.InterpretationThe incidence of clandestine, potentially unsafe induced abortion in Peru is as high as or higher than the rates in many countries where induced abortion is legal and safe. The provision of contraception and safer-sex education to those who require it needs to be greatly improved and could potentially reduce the rate of induced abortion.
| S-EPMC2630358 | biostudies-literature
Project description:The frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa. Moreover, available studies have used very small sample sizes to provide reliable estimates of the frequencies of these variants in the general population. We determined the frequency of the two APOL1 risk alleles (G1 and G2) and investigated their association with renal traits in a relatively large sample of mixed-ancestry South Africans. APOL1 risk variants (G1: rs60910145 and rs73885319; G2: rs71785313) were genotyped in 859 African mixed ancestry individuals using allele-specific TaqMan technology. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.The frequencies of rs73885319, rs60910145 and rs71785313 risk alleles were respectively, 3.6%, 3.4%, and 5.8%, resulting in a 1.01% frequency of the APOL1 two-risk allele (G1:G1 or G1:G2 or G2:G2). The presence of the two-risk allele increased serum creatinine with a corresponding reduction in eGFR (either MDRD or CKD-EPI based). In dominant and log-additive genetic models, significant associations were found between rs71785313 and systolic blood pressure (both p ? 0.025), with a significant statistical interaction by diabetes status, p = 0.022, reflecting a negative non-significant effect in nondiabetics and a positive effect in diabetics.Although the APOL1 variants are not common in the mixed ancestry population of South Africa, the study does provide an indication that APOL1 variants may play a role in conferring an increased risk for renal and cardiovascular risk in this population.
| S-EPMC4482162 | biostudies-literature
Project description:OBJECTIVE:Among African Americans, the apolipoprotein L1 (APOL1) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease. APPROACH AND RESULTS:In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the APOL1 high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with APOL1 genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m2) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between APOL1 genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83-1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77-1.76) models; however, in using an additive model, APOL1 high-risk variants were associated with increased cardiovascular mortality. CONCLUSIONS:Among African Americans with hypertension-attributed chronic kidney disease, APOL1 risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.
| S-EPMC5570668 | biostudies-literature
Project description:Hepatitis B virus (HBV) infection is still a concern in vulnerable populations. In a study performed by our team in 1999-2003 in two Afro-Brazilian communities, Furnas dos Dionísios (FD) and São Benedito (SB), high prevalence rates of HBV exposure (42.7% and 16.0%, respectively), high susceptibility to HBV (55.3% and 63.0%) and low HBV vaccination like profile rates (2.0% and 21.0%) were observed. In 2015-2016, we reassessed HBV epidemiological and molecular features in these two communities to verify the impact of health actions adopted in the last years. The prevalence rate of HBV exposure among the enrolled 331 subjects was 35.3% in FD and 21.8% in SB. HBV chronic infection (5.8% in FD, 4.9% in SB) remained high. The rate of HBV vaccination like profile increased from 10.7% to 43.5% (2.0% to 45.9% in FD, 21.0% to 39.5% in SB) while susceptible subjects declined from 58.9% to 26.3% (55.3% to 18.8% in FD, 63.0% to 38.7% in SB). Among 18 HBsAg positive samples, 13 were successfully sequenced (pre-S/S region). Phylogenetic analyses showed that all isolates belong to HBV subgenotype A1, clustering within the Asian-American clade. Despite the maintenance of high prevalence rate of HBV exposure over these 13 years of surveillance, significant improvements were observed, reinforcing the importance of facilitated HBV vaccination to difficult-to-access population to close gaps in prevention.
| S-EPMC7174315 | biostudies-literature
Project description:IntroductionAPOL1 G1 and G2 nephropathy-risk variants cause mitochondrial dysfunction and contribute to kidney disease. Analyses were performed to determine the genetic regulation of APOL1 and elucidate potential mechanisms in APOL1-nephropathy.MethodsA global gene expression analysis was performed in human primary renal tubule cell lines derived from 50 African American individuals. Follow-up gene knock out, cell-based rescue, and microscopy experiments were performed.ResultsAPOL1 genotypes did not alter APOL1 expression levels in the global gene expression analysis. Expression quantitative trait locus (eQTL) analysis in polyinosinic-polycytidylic acid (poly IC)-stimulated renal tubule cells revealed that single nucleotide polymorphism (SNP) rs513349 adjacent to BAK1 was a trans eQTL for APOL1 and a cis eQTL for BAK1; APOL1 and BAK1 were co-expressed in cells. BAK1 knockout in a human podocyte cell line resulted in diminished APOL1 protein, supporting a pivotal effect for BAK1 on APOL1 expression. Because BAK1 is involved in mitochondrial dynamics, mitochondrial morphology was examined in primary renal tubule cells and HEK293 Tet-on cells of various APOL1 genotypes. Mitochondria in APOL1 wild-type (G0G0) tubule cells maintained elongated morphology when stimulated by low-dose poly IC, whereas those with G1G1, G2G2, and G1G2 genotypes appeared to fragment. HEK293 Tet-on cells overexpressing APOL1 G0, G1, and G2 were created; G0 cells appeared to promote mitochondrial fusion, whereas G1 and G2 induced mitochondrial fission. The mitochondrial dynamic regulator Mdivi-1 significantly preserved cell viability and mitochondrial cristae structure and reversed mitochondrial fission induced by overexpression of G1 and G2.ConclusionResults suggest the mitochondrial fusion/fission pathway may be a therapeutic target in APOL1-nephropathy.
| S-EPMC7271005 | biostudies-literature
Project description:Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors.The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLA match, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed.Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 × 10), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant.Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.
| S-EPMC4684443 | biostudies-literature
Project description:BackgroundThis study describes chronic kidney disease of uncertain aetiology (CKDu), which cannot be attributed to diabetes, hypertension or other known aetiologies, that has emerged in the North Central region of Sri Lanka.MethodsA cross-sectional study was conducted, to determine the prevalence of and risk factors for CKDu. Arsenic, cadmium, lead, selenium, pesticides and other elements were analysed in biological samples from individuals with CKDu and compared with age- and sex-matched controls in the endemic and non-endemic areas. Food, water, soil and agrochemicals from both areas were analysed for heavy metals.ResultsThe age-standardised prevalence of CKDu was 12.9% (95% confidence interval [CI] = 11.5% to 14.4%) in males and 16.9% (95% CI = 15.5% to 18.3%) in females. Severe stages of CKDu were more frequent in males (stage 3: males versus females = 23.2% versus 7.4%; stage 4: males versus females = 22.0% versus 7.3%; P < 0.001). The risk was increased in individuals aged >39 years and those who farmed (chena cultivation) (OR [odds ratio] = 1.926, 95% CI = 1.561 to 2.376 and OR = 1.195, 95% CI = 1.007 to 1.418 respectively, P < 0.05). The risk was reduced in individuals who were male or who engaged in paddy cultivation (OR = 0.745, 95% CI = 0.562 to 0.988 and OR = 0.732, 95% CI = 0.542 to 0.988 respectively, P < 0.05). The mean concentration of cadmium in urine was significantly higher in those with CKDu (1.039 μg/g) compared with controls in the endemic and non-endemic areas (0.646 μg/g, P < 0.001 and 0.345 μg/g, P < 0.05) respectively. Urine cadmium sensitivity and specificity were 70% and 68.3% respectively (area under the receiver operating characteristic curve = 0.682, 95% CI = 0.61 to 0.75, cut-off value ≥0.397 μg/g). A significant dose-effect relationship was seen between urine cadmium concentration and CKDu stage (P < 0.05). Urine cadmium and arsenic concentrations in individuals with CKDu were at levels known to cause kidney damage. Food items from the endemic area contained cadmium and lead above reference levels. Serum selenium was <90 μg/l in 63% of those with CKDu and pesticides residues were above reference levels in 31.6% of those with CKDu.ConclusionsThese results indicate chronic exposure of people in the endemic area to low levels of cadmium through the food chain and also to pesticides. Significantly higher urinary excretion of cadmium in individuals with CKDu, and the dose-effect relationship between urine cadmium concentration and CKDu stages suggest that cadmium exposure is a risk factor for the pathogensis of CKDu. Deficiency of selenium and genetic susceptibility seen in individuals with CKDu suggest that they may be predisposing factors for the development of CKDu.
| S-EPMC3765913 | biostudies-literature
Project description:BACKGROUND:Child and adolescent mental health has scarcely been studied in developing countries, though it is an important aspect of health. Mental health problems in youth often continue into adulthood if not diagnosed or treated in time. METHODS:The Sistema de Evaluación de Niños y Adolescentes (SENA) [Child and Adolescent Evaluation System] was used to evaluate mental health indicators in a sample of students in Northern Chile. Two age-appropriate versions of the assessment were applied to a total sample of 5043 students, which included an elementary education sample of 1953 schoolchildren from fourth grade through sixth grade (ages 8 to 13?years), and a Secondary School sample of 3090 schoolchildren from seventh grade (the last year of elementary school) through the last year of Secondary school (senior high school) (ages 12 to 19?years). For each group, the version of the assessment used was determined by the students' grade level. Both samples included municipal, government-subsidized, and private schools. RESULTS:In this student population, depression, anxiety, and behavioral disorders were the main mental health problems identified, and indicators revealed a progressive increase in cases over the years, coinciding with the global epidemiological scenario. Males showed a greater presence of externalizing behaviors related to mental health problems associated with aggression and defiant behavior. However, females showed the highest number of mental health issues overall, especially regarding problems related to internalization. There are significant differences between school types. CONCLUSIONS:Our sample population analysis indicates that early intervention is necessary for the diagnosis and treatment of youth, with the goal of reducing the probability that psychiatric disorders will be prolonged, evolving, and worsening in adulthood.
| S-EPMC7059272 | biostudies-literature