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Novel sequence variants in the human xylosyltransferase I gene and their role in diabetic nephropathy
Author(s) -
Bahr C.,
Schön S.,
Kuhn J.,
Groop P. H.,
Parkkonen M.,
Wessman M.,
Kleesiek K.,
Götting C.
Publication year - 2006
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2006.01899.x
Subject(s) - medicine , nephropathy , sequence (biology) , diabetic nephropathy , gene , computational biology , diabetes mellitus , bioinformatics , genetics , endocrinology , biology
Aims Decreased content of heparan sulphate proteoglycans (HSPGs) is a characteristic of the glomerular basement membrane (GBM) in diabetes and contributes to the development of diabetic nephropathy (DN). Xylosyltransferase I (XT‐I) is the chain‐initiating enzyme involved in the biosynthesis of HSPGs. This study investigated a possible association between XYLT‐I sequence variants and susceptibility to DN. Methods Screening of all XYLT‐I exons was performed in 74 caucasians with Type 1 diabetes (48 with and 26 without DN) and in 13 non‐diabetic control subjects using denaturing high‐performance liquid chromatography. Results Fifteen XYLT‐I sequence variants were identified. Of these, six were previously unknown. There were significant differences in the allele frequencies of the three polymorphisms (c.343G→T (p.A115S), IVS3+10C→T, IVS3+30G→C) in Type 1 diabetic patients and healthy controls. Conclusions The occurrence of DN is independent of the XYLT‐I variants detected in our study. However, three XYLT‐I polymorphisms may be linked to Type 1 diabetes. Since we have previously proposed that one of these polymorphisms was not associated with Type 1 diabetes (Schön S et al. Kidney Int 2005; 68: 1483–1490), larger‐scale analysis is clearly necessary to pinpoint the significance of this mutation.