Serum sitosterol level predicting ABCG5 or ABCG8 genetic mutations
Serum sitosterol level predicting ABCG5 or ABCG8 genetic mutations
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DOI：
10.1016/j.cca.2020.04.003
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发表时间：
2020-08-01
影响因子：
5
通讯作者：
Kawashiri, Masa-aki
中科院分区：
文献类型：
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作者：
Kojima, Nobuko;Tada, Hayato;Kawashiri, Masa-aki
背景：目前，血清谷甾醇浓度大于10微克/毫升被认为是诊断谷甾醇血症的主要标准之一。方法：我们回顾了自2009-2018年来在我所接受调查的206例日本血脂异常患者(平均年龄46岁，男性94例)的血清谷甾醇水平和ABCG5或ABCG8基因突变情况。我们根据ABCG5或ABCG8基因致病突变的数量将受试者分为3组。比较两组间的血脂和血清谷甾醇水平，并验证双突变谷甾醇血症患者与其他突变患者的临界值。结果：共检出谷甾醇血症双突变患者8例(病变组)，单突变患者(携带者)26例，无突变患者(野生型对照)172例。具有双突变(受影响)的谷甾醇血症患者的血清谷甾醇水平显著高于任何其他组(45.2。与7.9微克/毫升，p=2.5×10(-2)，45.2比3.1微克/毫升，p=1.8×10(-2))。在此条件下，谷甾醇10 mU g/ml可较好地区分ABCG5或ABCG8基因双突变携带者(野生型对照)和非突变携带者(野生型对照)，而6例杂合性突变携带者谷甾醇水平均大于10 mU g/ml。受试者操作特征(ROC)分析预测双突变状态的最佳临界值为14.81 mU g/ml。
Background: Currently, serum concentrations of sitosterol above 10 mu g/ml are considered to be one of the major diagnostic criteria of sitosterolemia.Methods: We retrospectively investigated consecutive 206 Japanese dyslipidemic subjects (mean age = 46 yr, male n = 94) with the assessments of serum sitosterol level and the presence of ABCG5 or ABCG8 genetic mutations in our institute since 2009-2018. We divided the subjects into 3 groups based on the number of pathogenic mutations in ABCG5 or ABCG8 genes. We compared serum lipids and serum sitosterol among those groups, and tried to validate the cutoff value discriminating patients of sitosterolemia with double mutations from others.Results: We identified 8 individuals with sitosterolemia with double mutations (affected), 26 individuals with a single mutation (carrier), and 172 individuals without any mutations (wildtype control). Serum sitosterol level of patients with sitosterolemia with double mutations (affected) exhibited significantly higher than those of any other groups (45.2. vs. 7.9 mu g/ml, p = 2.5 x 10(-2), 45.2 vs. 3.1 mu g/ml, p = 1.8 x 10(-2)). Under these conditions, a cutoff value of sitosterol 10 mu g/ml could discriminate the patients with sitosterolemia with double mutations in ABCG5 or ABCG8 gene from no mutation carrier (wildtype control) perfectly, although 6 heterozygous mutation carries exhibited sitosterol level greater than 10 mu g/ml. Receiver-operating characteristic (ROC) analysis predicting double mutation status showed that the best cut-off value was 14.81 mu g/ml.Conclusion: We suggest a cutoff value of sitosterol 15 mu g/ml that shows higher positive predictive value than 10 mu g/ml.