Oh Kwangyeon, Yuk Minju, Yang Soyoun, Youn Jiyeong, Dong Qian, Wang Zhaoming, Song Nan
Department of Pharmacy, College of Pharmacy, Chungbuk National University, 194-21, Osongsaengmyeong-1 ro, Heungdeok-gu, Cheongju, 28160, Chungcheongbuk-do, Korea.
Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 38105, 262 Danny Thomas Place, Memphis, Tennessee, USA.
Sci Rep. 2025 Jan 2;15(1):189. doi: 10.1038/s41598-024-84466-1.
High-sensitivity C-reactive protein (hsCRP) is a representative biomarker of systemic inflammation and is associated with numerous chronic diseases. To explore the biological pathways and functions underlying chronic inflammation, we conducted a genome-wide association study (GWAS) and several post-GWAS analyses of the hsCRP levels. This study was performed on data from 71,019 Koreans and is one of the largest East Asian studies. Overall, 69 independent single nucleotide polymorphisms (SNPs) were identified, including 13 novel variants. The implicated genes and pathways are primarily involved in cholesterol metabolism and the immune response. A phenome-wide association study was performed based on a polygenic risk score (PRS) constructed using 69 hsCRP-associated SNPs. Notably, the alleles associated with higher hsCRP levels appeared to be associated with lower low-density lipoprotein cholesterol levels (P = 1.69 × 10, β = -1.47) and higher γ -glutamyl transpeptidase (P = 8.30 × 10, β = 0.84). It suggests that increase in genetically determined hsCRP may contribute to a decrease in cholesterol level and a strong oxidative environment in the blood vessel. Thus, individuals with higher hsCRP-PRS may have a greater risk of cardiovascular diseases. Our findings suggest the genetic association between cholesterol and hsCRP, as well as the clinical importance of hsCRP-PRS for predicting the potential risk of cardiovascular diseases.
高敏C反应蛋白（hsCRP）是全身炎症的代表性生物标志物，与多种慢性疾病相关。为了探索慢性炎症背后的生物学途径和功能，我们对hsCRP水平进行了全基因组关联研究（GWAS）和多项GWAS后分析。本研究基于71019名韩国人的数据进行，是最大的东亚研究之一。总体而言，共鉴定出69个独立的单核苷酸多态性（SNP），包括13个新变体。涉及的基因和途径主要参与胆固醇代谢和免疫反应。基于使用69个与hsCRP相关的SNP构建的多基因风险评分（PRS）进行了全表型关联研究。值得注意的是，与较高hsCRP水平相关的等位基因似乎与较低的低密度脂蛋白胆固醇水平相关（P = 1.69×10，β = -1.47）和较高的γ-谷氨酰转肽酶相关（P = 8.30×10，β = 0.84）。这表明遗传决定的hsCRP升高可能导致胆固醇水平降低和血管中强烈的氧化环境。因此，hsCRP-PRS较高的个体可能患心血管疾病的风险更大。我们的研究结果表明了胆固醇与hsCRP之间的遗传关联，以及hsCRP-PRS在预测心血管疾病潜在风险方面的临床重要性。
