C1GalT1的基因变异会导致IgA肾病易感性。

Genetic variant of C1GalT1 contributes to the susceptibility to IgA nephropathy.

作者信息

Pirulli Doroti, Crovella Sergio, Ulivi Sheila, Zadro Cristina, Bertok Sara, Rendine Sabina, Scolari Francesco, Foramitti Marina, Ravani Pietro, Roccatello Dario, Savoldi Silvana, Cerullo Giuseppina, Lanzilotta Salvatore Giovanni, Bisceglia Luigi, Zelante Leopoldo, Floege Jurgen, Alexopoulos Epstathios, Kirmizis Dimitrios, Ghiggeri Gian Marco, Frascà Giovanni, Schena Francesco Paolo, Amoroso Antonio

机构信息

Genetics Service, IRCCS Burlo Garofolo and Department of Reproductive and Developmental Sciences, University of Trieste, Trieste, Italy.

出版信息

J Nephrol. 2009 Jan-Feb;22(1):152-9.

PMID:19229831

Abstract

BACKGROUND

IgA nephropathy (IgAN) is a common form of primary glomerulonephritis characterized by diffuse glomerular mesangial IgA1 deposition that leads to mesangial proliferation and chronic glomerular inflammation. Analyses of serum IgA1 from IgAN patients revealed an abnormal galactosylation of the O-linked carbohydrate moieties of IgA that may be a result of altered activity of core 1 beta1,3-galactosyltransferase (C1GalT1). To evaluate the association between C1GalT1 single nucleotide polymorphisms (SNPs) and IgAN, we performed a case control study on cohorts from the Italian population.

METHODS

We sequenced C1GalT1 coding and promoter regions in 284 IgAN patients and 210 healthy controls. The functional role of 3' untranslated region (3'UTR) SNPs was studied using electrophoretic mobility shift assays and real-time quantitative PCR.

RESULTS

We analyzed 8 SNPs in the C1GalT1 gene: 5 SNPs were in the promoter region and 3 SNPs in the 3'UTR. The allele 1365G in the 3'UTR was significantly more frequent in IgAN patients than in healthy controls.

CONCLUSION

The 1365G allele and 1365G/G genotype seem to confer susceptibility to IgAN.

摘要

背景

IgA肾病（IgAN）是原发性肾小球肾炎的一种常见形式，其特征为弥漫性肾小球系膜IgA1沉积，导致系膜增生和慢性肾小球炎症。对IgAN患者血清IgA1的分析显示，IgA的O-连接碳水化合物部分存在异常糖基化，这可能是核心1β1,3-半乳糖基转移酶（C1GalT1）活性改变的结果。为了评估C1GalT1单核苷酸多态性（SNP）与IgAN之间的关联，我们对意大利人群队列进行了一项病例对照研究。