High genetic risk scores of SLIT3, PLEKHA5 and PPP2R2C variants increased insulin resistance and interacted with coffee and caffeine consumption in middle-aged adults.
Adult
Blood Glucose
/ metabolism
Caffeine
/ administration & dosage
Central Nervous System Stimulants
/ administration & dosage
Coffee
Female
Gene-Environment Interaction
Genome-Wide Association Study
Humans
Insulin
/ blood
Insulin Resistance
/ genetics
Intracellular Signaling Peptides and Proteins
/ genetics
Life Style
Male
Membrane Proteins
/ genetics
Middle Aged
Polymorphism, Single Nucleotide
Protein Phosphatase 2
/ genetics
Republic of Korea
Risk Assessment
Risk Factors
Coffee intake
GMDR
Insulin resistance
Insulin secretion
Metabolic syndrome
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
10
06
2018
revised:
19
09
2018
accepted:
20
09
2018
pubmed:
21
11
2018
medline:
15
3
2019
entrez:
21
11
2018
Statut:
ppublish
Résumé
Insulin resistance is a common feature of metabolic syndrome that may be influenced by genetic risk factors. We hypothesized that genetic risk scores (GRS) of SNPs that influence insulin resistance and signaling interact with lifestyles to modulate insulin resistance in Korean adults. Genome-wide association studies (GWAS) of subjects aged 40-65 years who participated in the Ansung/Ansan cohorts (8842 adults) in Korea revealed 52 genetic variants that influence insulin resistance. The best gene-gene interaction model was explored using the generalized multifactor dimensionality reduction (GMDR) method. GRS from the best model were calculated and the GRS were divided into low, medium and high groups. The best model for representing insulin resistance included SLIT3_rs2974430, PLEKHA5_rs1077044, and PPP2R2C_rs16838853. The odds ratios for insulin resistance were increased by 150% in the High-GRS group compared to the Low-GRS group. However, ORs for insulin secretion capacity, measured by HOMA-B, were not associated with GRS. Coffee and caffeine intake and GRS had an interaction with insulin resistance: In subjects with high coffee (≥10 cups/week) or caffeine intake (≥220 mg caffeine/day), insulin resistance was significantly elevated in the High-GRS group, but not in the Low-GRS. However, alcohol intake, smoking and physical activity did not have an interaction with GRS. Insulin secretion capacity was not significantly influenced by GRS when evaluating the adjusted odds ratios. Subjects with High-GRS may be susceptible to increased insulin resistance by 50% and its risk may be exacerbated by consuming more than 10 cups coffee/week or 220 mg caffeine/day.
Sections du résumé
BACKGROUNDS AND AIMS
Insulin resistance is a common feature of metabolic syndrome that may be influenced by genetic risk factors. We hypothesized that genetic risk scores (GRS) of SNPs that influence insulin resistance and signaling interact with lifestyles to modulate insulin resistance in Korean adults.
METHODS AND RESULTS
Genome-wide association studies (GWAS) of subjects aged 40-65 years who participated in the Ansung/Ansan cohorts (8842 adults) in Korea revealed 52 genetic variants that influence insulin resistance. The best gene-gene interaction model was explored using the generalized multifactor dimensionality reduction (GMDR) method. GRS from the best model were calculated and the GRS were divided into low, medium and high groups. The best model for representing insulin resistance included SLIT3_rs2974430, PLEKHA5_rs1077044, and PPP2R2C_rs16838853. The odds ratios for insulin resistance were increased by 150% in the High-GRS group compared to the Low-GRS group. However, ORs for insulin secretion capacity, measured by HOMA-B, were not associated with GRS. Coffee and caffeine intake and GRS had an interaction with insulin resistance: In subjects with high coffee (≥10 cups/week) or caffeine intake (≥220 mg caffeine/day), insulin resistance was significantly elevated in the High-GRS group, but not in the Low-GRS. However, alcohol intake, smoking and physical activity did not have an interaction with GRS. Insulin secretion capacity was not significantly influenced by GRS when evaluating the adjusted odds ratios.
CONCLUSIONS
Subjects with High-GRS may be susceptible to increased insulin resistance by 50% and its risk may be exacerbated by consuming more than 10 cups coffee/week or 220 mg caffeine/day.
Identifiants
pubmed: 30454882
pii: S0939-4753(18)30292-8
doi: 10.1016/j.numecd.2018.09.009
pii:
doi:
Substances chimiques
Blood Glucose
0
Central Nervous System Stimulants
0
Coffee
0
Insulin
0
Intracellular Signaling Peptides and Proteins
0
Membrane Proteins
0
PLEKHA5 protein, human
0
PPP2R2C protein, human
0
SLIT3 protein, human
0
Caffeine
3G6A5W338E
Protein Phosphatase 2
EC 3.1.3.16
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
79-89Informations de copyright
Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.