Skupien Jan, Kepka Grzegorz, Gorczynska-Kosiorz Sylwia, Gebska Anna, Klupa Tomasz, Wanic Krzysztof, Nowak Natalia, Borowiec Maciej, Sieradzki Jacek, Malecki Maciej T
Department and Chair of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.
Rev Diabet Stud. 2007 Winter;4(4):231-5. doi: 10.1900/RDS.2007.4.231. Epub 2008 Feb 10.
Apolipoprotein M (apoM) is a 26-kDa protein expressed mainly in the liver and kidneys. It is present predominantly in high-density lipoproteins (HDL). ApoM expression is influenced by the hepatocyte nuclear factor-1alpha (HNF-1alpha), which is a transcription factor associated with the pathogenesis of MODY. Some earlier data suggested that apoM levels were lower in the serum of HNF-1alpha MODY subjects, than in that of other diabetics and healthy controls. The aim of this study was to evaluate apoM as a biomarker for HNF-1alpha MODY. We included in this study 48 HNF-1alpha mutation carriers (40 diabetic patients and 8 subjects with normal glucose levels in the fasted state) from the Polish Nationwide Registry of MODY. In addition, we examined 55 T2DM patients and 55 apparently healthy volunteers who had normal fasting glucose levels. ApoM was measured by the sandwich dot-blot technique with recombinant apoM (Abnova) as a protein standard, mouse anti-human apoM monoclonal primary antibody and rat anti-mouse HRP-conjugated secondary antibody (BD Biosciences). Mean apoM level in the MODY group was 13.6 mug/ml, SD 1.9 (13.5 mug/ml, SD 1.7 in diabetic subjects and 13.9 mug/ml, SD 2.0 in non-diabetic mutation carriers respectively). In the T2DM group, mean apoM level was 13.7 mug/ml, SD 2.1, while it reached 13.8 mug/ml, SD 2.0 in healthy controls. There was no difference between apoM serum concentrations in all the study groups. In summary, our study showed no association between HNF-1alpha mutations resulting in MODY phenotype and apoM levels. Thus, we cannot confirm the clinical usefulness of apoM as a biomarker of HNF-1alpha MODY.
载脂蛋白M(apoM)是一种主要在肝脏和肾脏中表达的26 kDa蛋白质。它主要存在于高密度脂蛋白(HDL)中。apoM的表达受肝细胞核因子-1α(HNF-1α)影响,HNF-1α是一种与青少年发病的成年型糖尿病(MODY)发病机制相关的转录因子。一些早期数据表明,HNF-1α MODY患者血清中的apoM水平低于其他糖尿病患者和健康对照者。本研究的目的是评估apoM作为HNF-1α MODY生物标志物的价值。我们从波兰全国MODY登记处纳入了48名HNF-1α突变携带者(40名糖尿病患者和8名空腹血糖水平正常的受试者)。此外,我们检查了55名2型糖尿病(T2DM)患者和55名空腹血糖水平正常的明显健康志愿者。采用夹心斑点印迹技术,以重组apoM(Abnova)作为蛋白质标准品,小鼠抗人apoM单克隆一抗和大鼠抗小鼠辣根过氧化物酶(HRP)标记二抗(BD Biosciences)检测apoM。MODY组的平均apoM水平为13.6μg/ml,标准差为1.9(糖尿病受试者分别为13.5μg/ml,标准差为1.7,非糖尿病突变携带者为13.9μg/ml,标准差为2.0)。在T2DM组中,平均apoM水平为13.7μg/ml,标准差为2.1,而在健康对照组中达到13.8μg/ml,标准差为2.0。所有研究组的apoM血清浓度之间没有差异。总之,我们的研究表明,导致MODY表型的HNF-1α突变与apoM水平之间没有关联。因此,我们不能证实apoM作为HNF-1α MODY生物标志物的临床实用性。