A novel polymorphism of the human APRIL gene is associated with systemic lupus erythematosus
A novel polymorphism of the human APRIL gene is associated with systemic lupus erythematosus
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DOI：
10.1093/rheumatology/keg270
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发表时间：
2003-08-01
期刊：
影响因子：
5.5
通讯作者：
Horiuchi, T
中科院分区：
文献类型：
--
作者：
Koyama, T;Tsukamoto, H;Horiuchi, T
Objective.我们研究了肿瘤坏死因子家族新成员APRIL基因多态性与系统性红斑狼疮的相关性。为了通过外显子特异性聚合酶链反应-单链构象多态性（PCR-SSCP）分析检测人类APRIL基因的多态性，我们首先确定了人类APRIL基因的结构。根据APRIL基因组DNA序列设计了外显子特异性寡核苷酸引物。应用外显子特异性PCR-SSCP技术对148例SLE患者和146例正常对照者的APRIL基因外显子编码区进行分析，并对出现异常条带的外显子进行测序。人APRIL基因包含至少6个外显子和5个内含子，跨越基因组DNA的约2.8个碱基。通过外显子特异性PCR-SSCP，我们发现了两个新的多态性密码子67和96。两者均具有氨基酸取代：分别为G67 R和N96 S。在148例日本SLE患者中，只有67 G等位基因与SLE相关，等位基因频率为0.662，而146例未受影响的对照组为0.575（P=0.0302）。SLE患者中至少有一个67 G等位基因的频率（91.9%）显著高于正常对照组（80.1%）（P=0.0036）。APRIL的67 G等位基因可能是SLE发病的一个因素。
Objective. We investigated the association of gene polymorphisms in APRIL, a new member of the TNF family, with systemic lupus erythematosus.Methods. To detect polymorphisms of the human APRIL gene by exon-specific polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis, we first determined the structure of the human APRIL gene. We designed exon-specific oligonucleotide primers according to the genomic DNA sequence of APRIL. All of the coding regions in exons of the APRIL gene were analysed by exon-specific PCR-SSCP in 148 SLE patients and 146 unaffected controls, then the nucleotide sequences of exons that displayed aberrant bands were determined.Results. The human APRIL gene comprised at least six exons with five introns, spanning approximately 2.8 kilobases of the genomic DNA. By exon-specific PCR-SSCP, we identified two novel polymorphisms at codons 67 and 96. Both had amino acid substitutions: G67R and N96S respectively. Only the 67G allele was associated with SLE in 148 Japanese SLE patients, with allele frequency 0.662 compared with 0.575 for 146 unaffected controls (P=0.0302). The frequency of the individuals who possessed at least one 67G allele in SLE patients (91.9%) was significantly higher than that in the unaffected controls (80.1%) (P=0.0036).Conclusion. The 67G allele of APRIL may be a contributing factor in the pathogenesis of SLE.