2024-03-29T15:23:18Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/85052022-10-25T09:18:09Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Murphy, Aoife M
author
Smith, Caren E
author
Murphy, Leanne M
author
Follis, Jack L
author
Tanaka, Toshiko
author
Richardson, Kris
author
Noordam, Raymond
author
Lemaitre, Rozenn N
author
Kähönen, Mika
author
Dupuis, Josée
author
Voortman, Trudy
author
Marouli, Eirini
author
Mook-Kanamori, Dennis O
author
Raitakari, Olli T
author
Hong, Jaeyoung
author
Dehghan, Abbas
author
Dedoussis, George
author
de Mutsert, Renée
author
Lehtimäki, Terho
author
Liu, Ching-Ti
author
Rivadeneira, Fernando
author
Deloukas, Panagiotis
author
Mikkilä, Vera
author
Meigs, James B
author
Uitterlinden, Andre
author
Ikram, Mohammad A
author
Franco, Oscar H
author
Hughes, Maria
author
O' Gaora, Peadar
author
Ordovas, Jose M
author
Roche, Helen M
author
2019-08-20
SCOPE: Insulin resistance (IR) and inflammation are hallmarks of type 2 diabetes (T2D). The nod-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a metabolic sensor activated by saturated fatty acids (SFA) initiating IL-1β inflammation and IR. Interactions between SFA intake and NLRP3-related genetic variants may alter T2D risk factors. METHODS: Meta-analyses of six Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 19 005) tested interactions between SFA and NLRP3-related single-nucleotide polymorphisms (SNPs) and modulation of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance. RESULTS: SFA interacted with rs12143966, wherein each 1% increase in SFA intake increased insulin by 0.0063 IU mL-1 (SE ± 0.002, p = 0.001) per each major (G) allele copy. rs4925663, interacted with SFA (β ± SE = -0.0058 ± 0.002, p = 0.004) to increase insulin by 0.0058 IU mL-1 , per additional copy of the major (C) allele. Both associations are close to the significance threshold (p < 0.0001). rs4925663 causes a missense mutation affecting NLRP3 expression. CONCLUSION: Two NLRP3-related SNPs showed potential interaction with SFA to modulate fasting insulin. Greater dietary SFA intake accentuates T2D risk, which, subject to functional validation, may be further elaborated depending on NLRP3-related genetic variants.
Mol Nutr Food Res. 2019: e1900226
1613-4125
http://hdl.handle.net/20.500.12105/8505
31432628
10.1002/mnfr.201900226
1613-4133
Molecular nutrition & food research
Cohorts for Heart and Ageing Research in Genomic Epidemiology consortium
NLRP3 inflammasomes
Genome-wide interaction studies
Insulin resistance
Meta-analyses
Saturated fats
Potential Interplay between Dietary Saturated Fats and Genetic Variants of the NLRP3 Inflammasome to Modulate Insulin Resistance and Diabetes Risk: Insights from a Meta-Analysis of 19 005 Individuals