Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/8505
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
Murphy, Aoife M | Smith, Caren E | Murphy, Leanne M | Follis, Jack L | Tanaka, Toshiko | Richardson, Kris | Noordam, Raymond | Lemaitre, Rozenn N | Kähönen, Mika | Dupuis, Josée | Voortman, Trudy | Marouli, Eirini | Mook-Kanamori, Dennis O | Raitakari, Olli T | Hong, Jaeyoung | Dehghan, Abbas | Dedoussis, George | de Mutsert, Renée | Lehtimäki, Terho | Liu, Ching-Ti | Rivadeneira, Fernando | Deloukas, Panagiotis | Mikkilä, Vera | Meigs, James B | Uitterlinden, Andre | Ikram, Mohammad A | Franco, Oscar H | Hughes, Maria | O' Gaora, Peadar | Ordovas, Jose M CNIC | Roche, Helen M
Mol Nutr Food Res. 2019: e1900226
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.
Cohorts for Heart and Ageing Research in Genomic Epidemiology consortium | NLRP3 inflammasomes | genome-wide interaction studies | insulin resistance | meta-analyses | saturated fats
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