The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. Six protein-coding variants were studied, including three novel variants (L22V, R287T, and G410C) and three previously reported variants (R36S, Q259K, and H331P). The cDNA sequences encoding each amino acid variant and the wild-type CYP4V2 protein were cloned into the pcDNA/PDEST40 expression vector and transfected into eukaryotic 293T cells for overexpression of the CYP4V2 coding variants. CYP4V2 H331P and CYP4V2 G410C exhibited significant decreases in activity for lauric acid oxidation (20-30% of wild-type activity), when compared to the wildtype, which was correlated with low expression of CYP4V2 H331P and G410C substituted proteins. The other four CYP4V2 amino variants were comparable to wild-type CYP4V2 for lauric acid metabolism. The CYP4V2 H331P and G410C substitutions were predicted to cause a structural change through in silico analysis. In conclusion, the present study provides functional information about CYP4V2 genetic variants. These findings will be valuable for interpreting individual variations in phenotypes associated with CYP4V2 function in the clinical setting.

中文翻译：

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月桂酸代谢活性降低的CYP4V2遗传变异的鉴定和功能表征

本研究的目的是确定 CYP4V2 遗传变异并表征其功能后果。共鉴定出 26CYP4V2 遗传变异，包括 60 名随机选择的健康受试者的 7 种新变异。研究了六个蛋白质编码变体，包括三个新变体（L22V、R287T 和 G410C）和三个先前报道的变体（R36S、Q259K 和 H331P）。将编码每个氨基酸变体和野生型 CYP4V2 蛋白的 cDNA 序列克隆到 pcDNA/PDEST40 表达载体中，并转染到真核 293T 细胞中，用于过表达 CYP4V2 编码变体。与野生型相比，CYP4V2 H331P 和 CYP4V2 G410C 的月桂酸氧化活性显着降低（野生型活性的 20-30%），这与 CYP4V2 H331P 和 G410C 取代蛋白的低表达相关。其他四种 CYP4V2 氨基变体在月桂酸代谢方面与野生型 CYP4V2 相当。通过计算机分析预测 CYP4V2 H331P 和 G410C 取代会引起结构变化。总之，本研究提供了有关 CYP4V2 遗传变异的功能信息。这些发现对于解释临床环境中与 CYP4V2 功能相关的表型的个体差异是有价值的。本研究提供了有关 CYP4V2 遗传变异的功能信息。这些发现对于解释临床环境中与 CYP4V2 功能相关的表型的个体差异是有价值的。本研究提供了有关 CYP4V2 遗传变异的功能信息。这些发现对于解释临床环境中与 CYP4V2 功能相关的表型的个体差异是有价值的。