2026-06-14T03:31:50Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/85052024-09-27T08:08:03Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

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 10.1002/mnfr.201900226 1613-4133 1613-4125 Molecular nutrition & food research 31432628 http://hdl.handle.net/20.500.12105/8505 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