4. Polymorphisms in the gene coding for core1 beta 1.3 galactosyltransferase T1 contribute to the genetic susceptibility to IgA nephropathy

Record Control Number: Quality Validation Date: Update Date:
33336 2004-07-29 2004-11-29

Abstract: IgA nephropathy (IgAN [MIM 161950]) is a common form of primary glomerulonephritis characterised by diffuse glomerular mesangial IgA1 deposition that leads to mesangial proliferation and chronic glomerular inflammation. Analysis of serum IgA1 from IgAN patients revealed an abnormally galactosylation of the O-linked carbohydrate moieties of IgA.

It may be hypothesised that the abnormal glycosylation of the hinge region glycans could result from a reduced quantity or enzymatic activity of the Core1 beta 1,3- Galactosyltransferase. Recently, C1GALT1 gene coding for this molecule has been characterised.

In order to evaluate the association between C1GALT1 and IgAN, we performed a case control study among the Italian population. We sequenced C1GALT1 coding and promoter regions in 196 IgAN patients and 234 healthy controls. We identified 8 single nucleotide polymorphisms (SNPs) two of which were never described: 5 were in the promoter region (-796T/C, -784G/T, -511G/A, -392G/T, -353insC) and 3 in the 3UTR (1365G/A, 1484T/A, 1513T/A).

Comparing allelic frequencies of C1GALT1 SNPs between patients and controls, we evidenced that allele 1365G in 3UTR was significantly more frequent in IgAN patients than in healthy controls (Chi-square =14.68, p = 0.0001, pc = 0.008, odds ratio 2.47 [95% CI: 1.54-3.97]).

For the linkage disequilibrium analysis, and in order to calculate the haplotype frequencies, we processed genotypes data with Genotype Transposer and Arlequin softwares.

The promoter CGATW haplotype was significantly less frequent in IgAN patients than in healthy controls (Chi-square =6.76, p = 0.009, pc = 0.05 odds ratio 0.564 [95% CI: 0.365-0.872]).

The genotype 1365G/G confers susceptibility to IgAN (Chi-square =12.26, p = 0.0005, pc= 0.004, odds ratio 2.51 [95% CI: 1.48-4.24]) but it is not associated with the progression of the disease. The role of this SNP in the pathogenesis of IgAN has been investigated by Real-time quantitative PCR experiments that have shown reduced expression of C1GALT1 in homozygous 1365 G/G (mean ratio +/-SD: 1,4+/1,46) individuals in respect to those with other genotypes (mean ratio +/- SD: 2,96+/-2,5; unpaired t test p value =0.0295).

The results of this study suggest that C1GALT1 plays a possible role as a pathogenetic factor for IgAN.

Subject Descriptors: Genetics
Subject Index Codes: Life Sciences
Market Applications: Health monitoring, care
Stage Description: Scientific knowledge (applied research).
Collaboration Sought: Further research or development support; Information exchange/Training; Private-public partnership
Collaboration Detail: Other investigators invited in genetic studies of IgA Nephropathy are welcome for further collaborations. In addition, SMEs interested in this data are welcome to produce a specific kit.
Sources of Support: CEC
Remarks: Results e TIP
Intellectual Property Rights: Copyright(s) registered

This promising result was selected to be showcased as an offer
Genetic research on IgA nephropathy

Contact Details
Contact Name: AMOROSO, Antonio (Professor)
Position: Head of Genetics Unit
Contact Organisation: Dipartimento di Scienze della Riproduzione e dello sviluppo University of Trieste
Address: Via dellIstria 65/l
City: Trieste
Region: NORD EST
Postcode: 34137
Country: ITALY
Telephone Number: +39-040-3785275
Fax Number: +39-040-3785540

Related Programme(s) / Project(s)
Project Reference
Project Title
LIFE QUALITY QLG1-CT-2000-00464 Development of a genomic DNA bank of iga nephropathy (igan) patients and family members. New trends in genetics for the early diagnosis of familial igan

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