セルロプラスミン遺伝子異常と糖尿病との関連

Cp基因已被证明是遗传性铜蓝蛋白（Cp）缺乏症（HCD）的原因，这是一种常染色体隐性遗传疾病，其特征是神经系统异常。在许多HCD病例中，糖尿病（DM）是该病的首发症状，10 - 20年后在40 - 60岁时发生神经系统异常。仅在一个等位基因中携带缺陷Cp基因的个体（杂合子）被认为是无症状的。但是，我们假设在这些个体中，与HCD相关的致病变化发生缓慢，并且仅在老年时达到发展为DM的水平。为了证明这一点，我们对我院门诊（约320人）和附属医院（约800人）的所有DM患者进行了血清Cp水平测定，发现6例此类病例。Cp基因的遗传学分析表明其中一人确实存在基因突变。分析这些患者的临床和实验室特征，我们发现他们有轻度HCD的脑MRI表现。这些发现有力地支持了我们的假设。此外，我们发现血清Cp和血液HbA 1c水平呈正相关，表明高血糖是血清Cp升高的一个因素。血清Cp水平随着年龄的增长而增加，但这种增加在DM中减弱。这些发现可能有助于理解血清Cp与DM的关系，尽管可能需要进一步的研究，如使用Cp基因敲除小鼠的研究来澄清这些。

The Cp gene has been shown as responsible for hereditary ceruloplasmin (Cp) deficiency (HCD), which is an autosomal recessive disease characterized by neurological abnormalities. In many HCD cases, Diabetes mellitus (DM) was the first symptom of the disease, and 10 - 20 years later at age 40 - 60 the neurological abnormalities occurred. The individuals carrying the defective Cp genes in one allele only (heterozygote) have been considered as asymptomatic. But, we made hypothesis that in these individuals the pathogenic changes related to HCD occur slowly, and reach to the levels only to develop DM at late age. To prove this, we have measured serum Cp levels in all DM out-patients in our clinic (about 320 individuals) and affiliated hospitals (about 800 individuals), and found 6 such cases. Genetic analysis of Cp gene revealed that one of them had indeed the gene mutation. Analysis of clinical and laboratorical features of these patients lead us to find that they have brain MRI findings specific to HCD in mild form. These findings together strongly support our hypothesis. Furthermore, we found positive correlation between serum Cp and blood HbA1c levels, indicating that hyperglycemia is a factor for an increase of serum Cp. Serum Cp levels increase with aging, but this increase was attenuated in DM.These findings may contribute to the understanding of the relationship of serum Cp to DM, although further studies such as study using knock out mouse of Cp may be needed to clarify these.