Association of Genetic Variants for Plasma LRG1 With Rapid Decline in Kidney Function in Patients With Type 2 Diabetes.
J Clin Endocrinol Metab
; 106(8): 2384-2394, 2021 07 13.
Article
en En
| MEDLINE
| ID: mdl-33889958
ABSTRACT
CONTEXT Elevated levels of plasma leucine-rich α-2-glycoprotein 1 (LRG1), a component of transforming growth factor beta signaling, are associated with development and progression of chronic kidney disease in patients with type 2 diabetes (T2D). However, whether this relationship is causal is uncertain. OBJECTIVES:
To identify genetic variants associated with plasma LRG1 levels and determine whether genetically predicted plasma LRG1 contributes to a rapid decline in kidney function (RDKF) in patients with T2D. DESIGN ANDPARTICIPANTS:
We performed a genome-wide association study of plasma LRG1 among 3694 T2D individuals [1881 (983 Chinese, 420 Malay, and 478 Indian) discovery from Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes cohort and 1813 (Chinese) validation from Diabetic Nephropathy cohort]. One- sample Mendelian randomization analysis was performed among 1337 T2D Chinese participants with preserved glomerular filtration function [baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2)]. RDKF was defined as an eGFR decline of 3 mL/min/1.73 m2/year or greater.RESULTS:
We identified rs4806985 variant near LRG1 locus robustly associated with plasma LRG1 levels (meta Pâ =â 6.66â ×â 10-16). Among 1337 participants, 344 (26%) developed RDKF, and the rs4806985 variant was associated with higher odds of RDKF (meta odds ratioâ =â 1.23, Pâ =â 0.030 adjusted for age and sex). Mendelian randomization analysis provided evidence for a potential causal effect of plasma LRG1 on kidney function decline in T2D (Pâ <â 0.05).CONCLUSION:
We demonstrate that genetically influenced plasma LRG1 increases the risk of RDKF in T2D patients, suggesting plasma LRG1 as a potential treatment target. However, further studies are warranted to elucidate underlying pathways to provide insight into diabetic kidney disease prevention.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
2_ODS3
Problema de salud:
1_doencas_nao_transmissiveis
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2_muertes_prematuras_enfermedades_notrasmisibles
Asunto principal:
Variación Genética
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Glicoproteínas
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Diabetes Mellitus Tipo 2
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Nefropatías Diabéticas
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Riñón
Tipo de estudio:
Clinical_trials
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2021
Tipo del documento:
Article
País de afiliación:
Singapur