Watanabe Yusuke, Inoue Tsutomu, Okada Hirokazu, Kotaki Shuhei, Kanno Yoshihiko, Kikuta Tomohiro, Suzuki Hiromichi
Department of Nephrology, Saitama Medical College.
Intern Med. 2006;45(16):947-51. doi: 10.2169/internalmedicine.45.1641. Epub 2006 Sep 15.
It is evident that leukocyte infiltration plays an important role in the pathogenesis of IgA nephropathy (IgAN). Selectin is one of the key adhesion molecules involved in leukocyte infiltration. Recent studies demonstrated a significant association between the selectin gene polymorphisms and susceptibility to IgAN. However, the impact of selectin gene polymorphisms on the progression to end-stage renal disease (ESRD) has not been studied.
To evaluate the influence of the selectin gene polymorphisms on the progression of IgAN, we designed specific primers for PCR genotyping and analyzed the association of selectin gene polymorphisms with the declining rate in renal function to its ESRD.
A total of 61 hemodialysis patients were enrolled in the study. The mean age at renal biopsy was 33.0+/-13.3 years old, and the mean age at the start of hemodialysis was 41.2+/-13.8 years old. The mean interval between the time points of renal biopsy and the start of hemodialysis was 8.2+/-6.5 years (ranging from 0 to 33 years). The interval was significantly longer in IgAN patients with a homoallele of C in C1402T, C1402/C1402, of the E-selectin gene, or a homoallele of C in C712T, C712/C712, of the L-selectin gene compared to others. The haplotype, which is a combination of C1402/C1402 and C712/C712, is able to distinguish the group that is at least a better prognosis than the severest prognostic one.
This study provides a possible association between the selectin gene polymorphisms and the rapid progression to ESRD in IgAN patients.
白细胞浸润在IgA肾病（IgAN）发病机制中起重要作用，这一点很明显。选择素是参与白细胞浸润的关键黏附分子之一。近期研究表明选择素基因多态性与IgAN易感性之间存在显著关联。然而，选择素基因多态性对终末期肾病（ESRD）进展的影响尚未得到研究。
为评估选择素基因多态性对IgAN进展的影响，我们设计了用于PCR基因分型的特异性引物，并分析了选择素基因多态性与肾功能下降至ESRD的速率之间的关联。
本研究共纳入61例血液透析患者。肾活检时的平均年龄为33.0±13.3岁，开始血液透析时的平均年龄为41.2±13.8岁。肾活检时间点与开始血液透析之间的平均间隔为8.2±6.5年（范围为0至33年）。与其他患者相比，E选择素基因C1402T位点C等位基因纯合子（C1402/C1402）或L选择素基因C712T位点C等位基因纯合子（C712/C712）的IgAN患者，其间隔时间显著更长。单倍型C1402/C1402和C712/C712的组合能够区分出预后至少比最差预后组更好的一组。
本研究揭示了选择素基因多态性与IgAN患者快速进展至ESRD之间可能存在的关联。
