急性间歇性卟啉病患者胆色素原脱氨基酶基因单核苷酸多态性分析

Three single nudeotide polymorphisms of porphobilinogen deaminase gene related to a Chinese patient with acute intermittent porphyria

目的探讨遗传因素在中国急性间歇性卟啉病（AIP）患者发病中的作用。方法记录1例AIP患者的临床资料，使用直接测序法分析胆色素原脱氨基酶（PBGD）基因和原卟啉原氧化酶（PPOX）基因所有外显子及外显子-内含子交界区。结果临床表现反复发生腹痛，与月经周期有关，伴随胆固醇及高密度脂蛋白胆固醇升高，卟啉定性试验阳性。基因筛查发现在PBGD基因中存在3个单核苷酸多态性（SNP）位点：4219T→G、8164C→A、9678G→A。3个位点在不同组合构成的单倍型与致病突变高度连锁。结论3个SNP位点可能是AIP患者的遗传学基础，为此病的早期诊断和遗传咨询提供了线索。

Objective To analyzed the role of genetic factors in pathogenesis of acute intermittent porphyria （AIP）. Methods Peripheral blood sample was collected from a Chinese female AIP patients, aged 36, to undergo direct sequencing to analyze all the exons and flanking introns of the porphobilinogen deaminase （PBGD） and protoporphyrinogen oxidase （PPOX） genes. The sequencing results were compared with the established human PBGD and PPOX sequences （GenBank Accession No. M95623; NC_0（0001.9）. Results Direct sequencing showed three kinds of single nucleotide polymorphism （SNP） in the PBGD gene. No mutation was found in the coding regions of either PBGD or PPOX gene. Conclusion The three SNPs may underlie the genetic defects of AIP in Chinese. SNP may serve as genetic markers for linkage analysis to track presymptomatic carriers in AIP families.