Department of Laboratory Medicine, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Targu Mures, Romania.
Department of Economic Science, Faculty of Economics and Law, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540566 Targu Mures, Romania.
Int J Mol Sci. 2024 Sep 18;25(18):10038. doi: 10.3390/ijms251810038.
Familial hypercholesterolemia (FH) is the most significant inherited risk factor for coronary heart disease (CHD). Current guidelines focus on monogenic FH, but the polygenic form is more common and less understood. This study aimed to assess the clinical utility of an 8-SNP LDLC polygenic score in a central Romanian cohort. The cohort included 97 healthy controls and 125 patients with premature (P)CHD. The weighted LDLC polygenic risk score (wPRS) was analyzed for associations with relevant phenotypic traits, PCHD risk, and clinical FH diagnosis. The wPRS positively correlated with LDLC and DLCN scores, and LDLC concentrations could be predicted by wPRS. A trend of increasing LDLC and DLCN scores with wPRS deciles was observed. A +1 SD increase in wPRS was associated with a 36% higher likelihood of having LDLC > 190 mg/dL and increases in LDLC (+0.20 SD), DLCN score (+0.16 SD), and BMI (+0.15 SD), as well as a decrease in HDLC (-0.14 SD). Although wPRS did not predict PCHD across the entire spectrum of values, individuals above the 90th percentile were three times more likely to have PCHD compared to those within the 10th or 20th percentiles. Additionally, wPRS > 45th percentile identified "definite" clinical FH (DLCN score > 8) with 100% sensitivity and 45% specificity. The LDLC polygenic score correlates with key phenotypic traits, and individuals with high scores are more likely to have PCHD. Implementing this genetic tool may enhance risk prediction and patient stratification. These findings, the first of their kind in Romania, are consistent with the existing literature.
家族性高胆固醇血症(FH)是冠心病(CHD)最重要的遗传危险因素。目前的指南侧重于单基因 FH,但多基因形式更为常见,也不太了解。本研究旨在评估 8 个 SNP LDLC 多基因评分在罗马尼亚中部队列中的临床应用价值。该队列包括 97 名健康对照者和 125 名早发性(P)CHD 患者。分析加权 LDLC 多基因风险评分(wPRS)与相关表型特征、PCHD 风险和临床 FH 诊断的相关性。wPRS 与 LDLC 和 DLCN 评分呈正相关,并且可以通过 wPRS 预测 LDLC 浓度。观察到 LDLC 和 DLCN 评分随 wPRS 十分位数的增加呈增加趋势。wPRS 增加 1 SD 与 LDLC > 190 mg/dL 的可能性增加 36%相关,并且与 LDLC(+0.20 SD)、DLCN 评分(+0.16 SD)和 BMI(+0.15 SD)增加以及 HDLC(-0.14 SD)减少相关。尽管 wPRS 不能预测整个值范围内的 PCHD,但与第 10 或 20 百分位的个体相比,位于第 90 百分位以上的个体发生 PCHD 的可能性高 3 倍。此外,wPRS > 45 百分位可以识别出具有 100%敏感性和 45%特异性的“明确”临床 FH(DLCN 评分> 8)。LDLC 多基因评分与关键表型特征相关,高分者更有可能发生 PCHD。实施这种遗传工具可能会增强风险预测和患者分层。这些发现是罗马尼亚首例此类发现,与现有文献一致。
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