Simó Josep M, Camps Jordi, Martín Silvia, Pedro-Botet Juan, Ferré Natalia, Gómez Frederic, Joven Jorge
Centre de Recerca Biomèdica, Institut de Recerca en Ciències de la Salut, Hospital Universitari de Sant Joan, Reus, Catalunya, Spain.
Clin Chem Lab Med. 2003 Oct;41(10):1340-4. doi: 10.1515/CCLM.2003.205.
The aim of the present study was to analyze, on a double-blind basis, the relationships between the apolipoprotein(a) (apo(a)) gene and protein size polymorphisms in healthy volunteers (n = 99) and patients with premature myocardial infarction (n = 91). Apo(a) genotypes were determined by pulse-field electrophoresis and phenotypes were separated by sodium dodecyl sulfate-agarose gel electrophoresis. Results showed that phenotyping overestimated apo(a) size with respect to genotyping (mean (SD) = 3.7 (3.4) kringle units; p < 0.001) in subjects with a double-band genotype, although both measurements were highly correlated (r = 0.83; p < 0.001). We also observed that the protein band in subjects with a single-band phenotype was related more closely to the smallest allele than to the largest allele band. The correlation of plasma lipoprotein(a) (Lp(a)) concentration was stronger with the phenotype than with the genotype. We hypothesize that post-translational modifications in the apo(a) molecule may be the most plausible explanation for the discrepancies observed. In conclusion, the present study highlights the dissimilarities between phenotyping and genotyping methods for the measurement of apo(a) size and suggests that laboratories should carefully consider these relationships and the transfer of results between such methodologies.
本研究旨在以双盲方式分析健康志愿者（n = 99）和早发心肌梗死患者（n = 91）中载脂蛋白(a)（apo(a)）基因与蛋白质大小多态性之间的关系。通过脉冲场电泳确定apo(a)基因型，并用十二烷基硫酸钠 - 琼脂糖凝胶电泳分离表型。结果显示，在具有双带基因型的受试者中，相对于基因分型，表型分析高估了apo(a)大小（均值（标准差）= 3.7（3.4）个kringle单位；p < 0.001），尽管两种测量方法高度相关（r = 0.83；p < 0.001）。我们还观察到，具有单带表型的受试者中的蛋白带与最小等位基因的关系比与最大等位基因带的关系更密切。血浆脂蛋白(a)（Lp(a)）浓度与表型的相关性强于与基因型的相关性。我们推测，apo(a)分子的翻译后修饰可能是观察到的差异的最合理的解释。总之，本研究突出了apo(a)大小测量中表型分析和基因分型方法之间的差异，并建议实验室应仔细考虑这些关系以及这些方法之间结果的转换。
