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 HbA1c levels were significantly higher in the high-wGRS group than in the other groups. The urinary 8-epi-PGF2α 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.
Bibliographical noteFunding Information:
The genotype data were produced using a Korean Chip (K-CHIP) available from the K-CHIP consortium. The K-CHIP was designed by the Center for Genome Science at the Korea National Institute of Health, Korea (4845–301, 3000–3031). The present study was financially supported by the Bio-Synergy Research Project (NRF-2012M3A9C4048762) and the Mid-Career Researcher Program (NRF-2016R1A2B4011662) of the Ministry of Science, ICT, and Future Planning through the National Research Foundation, Republic of Korea, and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C2686010115 and HI14C2686).
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