MedElevator
Войти в исследования Precision Diagnosis in APOL1 Kidney Disease With the p.N264K M1 Protective Variant.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Martinelli Elena, Ke Juntao, Khan Atlas, Wongboonsin Janewit, Vanderwall David R, Lim Tze Y, Santoriello Dominick, Gupta Yask, McNulty Michelle T, Koyama Satoshi, Puntambekar Sidhant, Bomback Andrew S, Canetta Pietro, Kretzler Matthias, Montini Giovanni, Morello William, Maggiore Umberto, Fiaccadori Enrico, Gesualdo Loreto, Ghiggeri Gian Marco, Oliveira Eduardo Araújo, Simoes E Silva Ana Cristina, Bendapudi Pavan K, Motelow Joshua, Garcia Christine K, Paul Dirk S, Petrovski Slavé, Goldstein David B, Friedman David J, Radhakrishnan Jai, Lin Fangming, Mohan Sumit, Appel Gerald B, Saleem Moin A, Natarajan Pradeep, Hildebrandt Friedhelm, Westland Rik, D'Agati Vivette D, Gbadegesin Rasheed, Gharavi Ali G, Pollak Martin R, Kiryluk Krzysztof, Sampson Matthew G, Sanna-Cherchi Simone, Columbia Genomics Consortium
Аннотация
OBJECTIVE: To test 2 hypotheses: (1) in patients with APOL1 high-risk (HR) genotype kidney disease with at least 1 G2 allele, M1 can distinguish APOL1 CKD from non-APOL1 CKD; (2) in people with APOL1 low-risk (LR) genotypes, M1 is independently associated with protection against FSGS and CKD.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective case-control study using data from 2 tertiary care hospitals (Columbia University Irving Medical Center and Mass General Brigham Biobank) and population-based data (the UK Biobank [UKB], Electronic Medical Records and Genomics [eMERGE-III], and All of Us [AoU]). Participants were individuals with a diagnosis of FSGS or steroid-resistant nephrotic syndrome (SRNS), individuals with CKD, and controls.
EXPOSURES: Exposures included the M1 variant (p.N264K) obtained from exome or genome sequencing data, sex, and genetic ancestry.
MAIN OUTCOME AND MEASURE: The main outcome was the presence or absence of kidney disease, defined as FSGS or non-FSGS CKD, compared with non-kidney disease controls. Association between the M1 variant and disease status was assessed using odds ratios (ORs).
RESULTS: A total of 107 696 individuals (54 994 [51.1%] female; 8779 [8.2%] with African ancestry, 78 475 [72.9%] with European ancestry, and 16 129 [15.0%] with multiethnic ancestry), including 3460 with FSGS or SRNS, 24 382 with non-FSGS CKD kidney disease, and 79 854 controls were enrolled in the discovery cohort. In the APOL1-HR group (1413 participants), M1 was significantly inversely associated with FSGS or SRNS cases compared with controls without kidney disease (OR, 0.20; 95% CI, 0.04-0.63; P = 3.69 × 10-3). Among individuals with CKD with APOL1-HR genotypes, M1 was 4 times more frequent in those whose CKD was not due to FSGS or SRNS. Importantly, electronic health record and biopsy review identified an alternative, non-APOL1 cause for CKD in nearly all APOL1-HR-M1 cases. There was no association between individuals with APOL1-LR genotypes with M1 and protection against CKD or FSGS.
CONCLUSIONS AND RELEVANCE: In this case-control study of 107 696 individuals, presence of an APOL1-HR genotype M1 was significantly associated with protection against kidney disease, suggesting that it may have a role as a genetic modifier. Patients with CKD with an APOL1-HR genotype and M1 should be evaluated for an alternative and potentially treatable cause of their CKD.