Muendlein Axel, Leiherer Andreas, Zach Christina, Brandtner Eva Maria, Fraunberger Peter, Drexel Heinz, Geiger Kathrin
Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Carinagasse 47, 6800, Feldkirch, Austria.
Medical Central Laboratories, Feldkirch, Austria.
Mol Biol Rep. 2019 Apr;46(2):2379-2385. doi: 10.1007/s11033-019-04696-9. Epub 2019 Feb 21.
Primary hypolactasia is the main cause of lactose intolerance in adults. It is strongly associated with the single genetic variant LCT-13910C>T, located upstream of the lactase encoding gene. Consequently, analysis of LCT-13910C>T has been recommended as a direct genetic test for the trait. The aim of our study was to develop a TaqMan probe based real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood, circumventing DNA isolation. The LCT-13910C>T variant was determined using the DirectBlood Genotyping PCR Kit (myPOLS Biotec, Konstanz, Germany) together with an in-house TaqMan primer-probe assay. Validity and specificity of the assay was evaluated using EDTA anti-coagulated whole blood samples and corresponding DNA samples. Results from real-time PCR were compared with results obtained by Sanger sequencing from 105 blinded whole blood samples. Validity and specificity of the assay using whole blood were comparable to those using purified genomic DNA as substrate in PCR. Genetic analysis of blood samples were in complete agreement with results obtained by Sanger sequencing. In conclusion, we present a reliable real-time PCR protocol for the detection of the LCT-13910C>T variant directly from whole blood further facilitating diagnosis of primary hypolactasia in symptomatic patients.
原发性乳糖酶缺乏是成人乳糖不耐受的主要原因。它与乳糖酶编码基因上游的单基因变体LCT-13910C>T密切相关。因此,建议对LCT-13910C>T进行分析,作为该性状的直接基因检测。我们研究的目的是开发一种基于TaqMan探针的实时PCR方法,用于直接从全血中检测LCT-13910C>T变体,无需进行DNA分离。使用DirectBlood基因分型PCR试剂盒(myPOLS Biotec,德国康斯坦茨)和内部TaqMan引物-探针检测法测定LCT-13910C>T变体。使用乙二胺四乙酸抗凝全血样本和相应的DNA样本评估该检测方法的有效性和特异性。将实时PCR结果与105份盲法全血样本的桑格测序结果进行比较。使用全血进行检测的有效性和特异性与使用纯化基因组DNA作为PCR底物的检测结果相当。血液样本的基因分析结果与桑格测序结果完全一致。总之,我们提出了一种可靠的实时PCR方法,用于直接从全血中检测LCT-13910C>T变体,进一步促进有症状患者原发性乳糖酶缺乏的诊断。