共存于载脂蛋白C-Ⅰ基因和伪基因之多态性Ile-11Met

目的：探讨可能存在于载脂蛋白 ＣⅠ（ａｐｏ ＣⅠ） 的基因突变或多态性及其频率和表型。方法：通过基因特异性引物和致突变分离聚合酶链反应（ Ｍ Ｓ Ｐ Ｃ Ｒ） 技术分离和扩增ａｐｏ ＣⅠ基因和伪基因片段，采用固相荧光直读法分别对其进行 Ｄ Ｎ Ａ 序列分析；对来自德国、意大利和日本人群的 Ｄ Ｎ Ａ 库样品进行基因型和表型及其相互关系的对比研究。结果：在受检者中首次发现ａｐｏ ＣⅠ基因一多态性位点，即其编码信号肽第１１ 位密码子的第３ 个核苷酸胞嘧啶突变为鸟嘌啶（ Ｃ→ Ｇ） ，从而导致该位置野生型的异亮氨酸突变为蛋氨酸（ Ｉｌｅ１１ Ｍｅｔ） 。该ａｐｏ ＣⅠ基因多态性的等位基因频率在德国和意大利人群中显著不同（１ ．６５ ％ ｖｓ ２ ．２８ ％ ， Ｐ＜ ０ ．０１） ，但在日本人 Ｄ Ｎ Ａ 库中未检出。该多态性还以高频率出现在ａｐｏ ＣⅠ伪基因中，但无论是存在于ａｐｏ ＣⅠ基因或伪基因之多态性 Ｉｌｅ１１ Ｍｅｔ，其杂合子或纯合子携带者的血脂参数与野生型比较均无明显改变。结论　揭示共存于ａｐｏ ＣⅠ基因和伪基因的多态性 Ｉｌｅ１１ Ｍｅｔ 在不同人群中的等位基因频率差异显著，但对血脂代谢无明显影响。

COEXISTENCE OF POLYMORPHISM ILe-11Met IN BOTH APOLIPOPROTEIN C-I GENE AND PSEUDOGENE

Objective: To explore possible mutations or polymorphisms in apolipoprotein C-I(apo C-I) gene and investigate their allele frequency and potenital phenotype.Methods: Using special gene primers and the technique of mutagenically-separated polymerase chain reaction(MS-PCR),the DNA fragments from apo C-I gene and pseudogene were amplified respectively. The DNA sequences of these fragments were analyzed by solid phase fluorescence technique.The comparative study on the relatonship of the identified polymorphism and its possible phenotype in German,Italian and Japanese populations were carried out.Results: A polymorphic site,i.e.the substitution of guanosine for cytoscine in codon -11 of apo C-I gene in the examined individuals was firstly identified,this nucleotide change leaded to the replacement of methionine (Met) for isoleucine(Ile) in the signal peptide(Ile-11Met).It was demonstrated that the mutant Met-allele frequencies in German and Italian populations were significantly different(1.65% vs 2.28%,P<0.01),but this genetic variant was not detected in Japanese individuals.This polymorphic site was also found in the correspondent position of apo C-I pseudogene in all three different populations with high frequencies.Furthermore, it was observed that the serum lipid parameters were not significantly different between the Met-allele carriers and wild type individuals in both apo C-I gene and pseudogene.Conclusion: It suggests that the polymorphic site coexists in both apo C-I gene and pseudogene with different allele frequencies but without affection to serum lipid metabolism.