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KMID : 0381120190410050537
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Genes and Genomics
2019 Volume.41 No. 5 p.537 ~ p.545
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Genetic risk score combining six genetic variants associated with the cellular NRF2 expression levels correlates with Type 2 diabetes in the human population
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Shin Jae-Hun
Lee Kyung-Mi
Shin Ji-Min
Kang Kui-Dong
Nho Chu-Won
Cho Yoon-Shin
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Abstract
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Background: Type 2 diabetes (T2D) is known as an inflammatory disease. NRF2 (Nuclear Factor Erythroid 2 Like2) encodes a transcription factor that binds to antioxidant response elements (AREs) and regulates the expression of genes involved in many antioxidant responses.
Objective: This study aimed to gain insight into individual anti-inflammatory activity to prevent T2D development in humans.
Methods: We performed a genome-wide association study (GWAS) to identify genetic variants influencing NRF2 expression in LCLs (lymphoblastoid cell lines) generated from 74 different individuals. Association analyses between T2D or its related traits and genetic risk score (GRS) calculated by combining genetic variants detected from GWAS for cellular NRF2 expression were performed using data from 8715 subjects. The T2D prediction model using GRS was evaluated by measuring the area under the curve (AUC) of the receiver operating characteristics (ROC) curve.
Results: Our GWAS identified six genetic variants (SNP) showing suggestive evidence of associations with cellular NRF2 expression (P?
Conclusion: This study highlights genetic variants associated with cellular NRF2 expression and suggests that the GRS of NRF2 expression-associated variants is likely to be a useful indicator of T2D development in the human population.
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KEYWORD
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Genome-wide association study (GWAS), Single nucleotide polymorphism (SNP), Genetic risk score (GRS), Type 2 diabetes (T2D), Inflammation, Oxidative stress, Nuclear factor erythroid 2 like2 (NRF2)
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