Current exposure to environmental pollutants in the general adult population of Kinshasa, Democratic Republic of Congo (DRC): A cross-sectional study

peer reviewedBackground : Environmental pollution is a serious public health problem because of its adverse effects on both human health and biodiversity. In Western countries, many human biomonitoring (HBM) studies are conducted to assess population exposure to pollutants. In contrast, the number of HBM studies in Africa is very low. Objective : To measure contamination by arsenic, lead, 4,4′-dichlorodiphenyldichloroethylene (4,4′-DDE) and polychlorobiphenyls (PCBs) in the adult population of Kinshasa and to identify the susceptible population. Methods : In the present work, we measured the contamination by arsenic in urine and lead in blood and by 4,4′-DDE and polychlorobiphenyls (PCBs) in serum in samples collected from 151 volunteers recruited in Kinshasa, the capital of the Democratic Republic of Congo (DRC). Results : The PCBs 180, -153 and −138 were detected in most samples with median concentrations of 0.04, 0.05 and 0.04 ng/ml, respectively. The median concentration of 4,4′-DDE was 0.83 ng/ml and 12.7% of our population showed contamination above the threshold of 3.675 ng/ml, which is associated with a significantly higher risk of cancer. Arsenic concentrations were also high (median: 48.1 μg/L in urine). Finally, exposure to lead is problematic: the median blood concentration was 54.9 μg/L, which is above the thresholds proposed by the WHO and the US CDC (50 μg/L and 35 μg/L respectively) to initiate clinical intervention, and 12.6% of the population had a lead level above 100 μg/L, which is associated with several health outcomes. Conclusions : Our results highlight the need for further HBM studies in Africa and should encourage the authorities of the DRC to implement laws and regulations to reduce pollution and population exposure

Etude des infections à virus BK chez les patients adultes recevant une allogreffe de cellules souches hématopoiétiques

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

International audienceAbstract Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE -ε4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1 -LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1- LoF variants, stratified by APOE-ε4 , derived from the Rotterdam study ( N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1- LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE -ε4-stratified SORL1- LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1- LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE -ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1- LoF variant carriers in case-control study data. Conclusions We conclude that SORL1- LoF variants should be interpreted in light of APOE genotypes for future clinical applications