Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Zaragoza, Spain; Instituto de Investigación Sanitaria de Aragón (IIS), San Juan Bosco 13, 50009 Zaragoza, Spain.
Clin Biochem. 2013 Dec;46(18):1804-7. doi: 10.1016/j.clinbiochem.2013.09.006. Epub 2013 Sep 20.
Human plasma chitotriosidase (ChT) activity, a biomarker for evaluating and monitoring Gaucher disease (GD), varies in the general population owing to variants in the CHIT1 gene. Our aim is to determine the frequency of the c.1049_1072dup24 (dup24) and p.G102S polymorphisms, their influence on plasma ChT activity, and its change with enzyme replacement therapy (ERT).
The study included 269 type1 GD patients. Genomic DNA was genotyped using PCR, restriction isotyping and agarose gel electrophoresis. ChT activity was measured with the 4-methylumbelliferyl-β-D-N,N',N″triacetylchitotrioside substrate at non-saturating concentrations at diagnosis, before beginning therapy and after one year on ERT.
Allele frequencies for dup24 and p.G102S were 0.22 and 0.27, respectively. Four percent of patients were homozygous and 37% heterozygous for dup24, and 9% homozygous and 37% heterozygous for p.G102S. The presence of dup24 and p.G102S polymorphisms in the CHIT1 gene significantly reduced plasma ChT activity in naïve patients. By contrast, the percentage of ChT activity decrease after one year of ERT was independent of the presence of these genetic variants.
This study indicates that genotyping for c.1049_1072dup24 and p.G102S polymorphisms will improve the interpretation of plasma chitotriosidase activity at diagnosis but, this is not mandatory for monitoring of enzyme replacement therapy.
人血浆壳三糖苷酶（ChT）活性是评估和监测戈谢病（GD）的生物标志物，由于 CHIT1 基因的变异，在普通人群中存在差异。我们的目的是确定 c.1049_1072dup24（dup24）和 p.G102S 多态性的频率、它们对血浆 ChT 活性的影响及其与酶替代治疗（ERT）的变化。
本研究纳入了 269 例 1 型 GD 患者。使用 PCR、限制酶切和琼脂糖凝胶电泳对基因组 DNA 进行基因分型。在诊断时、开始治疗前和 ERT 治疗 1 年后，使用 4-甲基伞形酮-β-D-N，N'，N″-三乙酰壳三糖苷作为非饱和浓度的底物测量 ChT 活性。
dup24 和 p.G102S 的等位基因频率分别为 0.22 和 0.27。4%的患者为 dup24 纯合子，37%为杂合子，9%的患者为 p.G102S 纯合子，37%为杂合子。CHIT1 基因中存在 dup24 和 p.G102S 多态性可显著降低初治患者的血浆 ChT 活性。相比之下，ERT 治疗 1 年后 ChT 活性下降的百分比与这些遗传变异无关。
本研究表明，CHIT1 基因 c.1049_1072dup24 和 p.G102S 多态性的基因分型将改善诊断时血浆壳三糖苷酶活性的解释，但这对于监测酶替代治疗并非必需。
