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Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress

We tested the hypothesis that the cumulative effects of common genetic variants related to elevated fasting glucose are collectively associated with oxidative stress. Using 25 single nucleotide polymorphisms (SNPs), a weighted genetic risk score (wGRS) was constructed by summing nine risk alleles ba...

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Autores principales: Kim, Minjoo, Kim, Minkyung, Huang, Limin, Jee, Sun Ha, Lee, Jong Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959868/
https://www.ncbi.nlm.nih.gov/pubmed/29777116
http://dx.doi.org/10.1038/s41598-018-26106-z
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author Kim, Minjoo
Kim, Minkyung
Huang, Limin
Jee, Sun Ha
Lee, Jong Ho
author_facet Kim, Minjoo
Kim, Minkyung
Huang, Limin
Jee, Sun Ha
Lee, Jong Ho
author_sort Kim, Minjoo
collection PubMed
description We tested the hypothesis that the cumulative effects of common genetic variants related to elevated fasting glucose are collectively associated with oxidative stress. Using 25 single nucleotide polymorphisms (SNPs), a weighted genetic risk score (wGRS) was constructed by summing nine risk alleles based on nominal significance and a consistent effect direction in 1,395 controls and 718 patients with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes. All the participants were divided into the following three groups: low-wGRS, middle-wGRS, and high-wGRS groups. Among the nine SNPs, five SNPs were significantly associated with IFG and type 2 diabetes in this Korean population. wGRS was significantly associated with increased IFG and newly diagnosed type 2 diabetes (p = 6.83 × 10(−14), odds ratio = 1.839) after adjusting for confounding factors. Among the IFG and type 2 diabetes patients, the fasting serum glucose and HbA(1c) levels were significantly higher in the high-wGRS group than in the other groups. The urinary 8-epi-PGF(2α) and malondialdehyde concentrations were significantly higher in the high-wGRS group than in the other groups. Moreover, general population-level instrumental variable estimation (using wGRS as an instrument) strengthened the causal effect regarding the largely adverse influence of high levels of fasting serum glucose on markers of oxidative stress in the Korean population. Thus, the combination of common genetic variants with small effects on IFG and newly diagnosed type 2 diabetes are significantly associated with oxidative stress.
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spelling pubmed-59598682018-05-24 Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress Kim, Minjoo Kim, Minkyung Huang, Limin Jee, Sun Ha Lee, Jong Ho Sci Rep Article We tested the hypothesis that the cumulative effects of common genetic variants related to elevated fasting glucose are collectively associated with oxidative stress. Using 25 single nucleotide polymorphisms (SNPs), a weighted genetic risk score (wGRS) was constructed by summing nine risk alleles based on nominal significance and a consistent effect direction in 1,395 controls and 718 patients with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes. All the participants were divided into the following three groups: low-wGRS, middle-wGRS, and high-wGRS groups. Among the nine SNPs, five SNPs were significantly associated with IFG and type 2 diabetes in this Korean population. wGRS was significantly associated with increased IFG and newly diagnosed type 2 diabetes (p = 6.83 × 10(−14), odds ratio = 1.839) after adjusting for confounding factors. Among the IFG and type 2 diabetes patients, the fasting serum glucose and HbA(1c) levels were significantly higher in the high-wGRS group than in the other groups. The urinary 8-epi-PGF(2α) and malondialdehyde concentrations were significantly higher in the high-wGRS group than in the other groups. Moreover, general population-level instrumental variable estimation (using wGRS as an instrument) strengthened the causal effect regarding the largely adverse influence of high levels of fasting serum glucose on markers of oxidative stress in the Korean population. Thus, the combination of common genetic variants with small effects on IFG and newly diagnosed type 2 diabetes are significantly associated with oxidative stress. Nature Publishing Group UK 2018-05-18 /pmc/articles/PMC5959868/ /pubmed/29777116 http://dx.doi.org/10.1038/s41598-018-26106-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Minjoo
Kim, Minkyung
Huang, Limin
Jee, Sun Ha
Lee, Jong Ho
Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress
title Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress
title_full Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress
title_fullStr Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress
title_full_unstemmed Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress
title_short Genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress
title_sort genetic risk score of common genetic variants for impaired fasting glucose and newly diagnosed type 2 diabetes influences oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959868/
https://www.ncbi.nlm.nih.gov/pubmed/29777116
http://dx.doi.org/10.1038/s41598-018-26106-z
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