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Genetic variation in the transforming growth factor-beta 1 gene is associated with susceptibility to IgA nephropathy
Karolinska Institute.
Karolinska University Hospital.
Karolinska Institute.
Sahlgrens University Hospital.
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2009 (English)In: NEPHROLOGY DIALYSIS TRANSPLANTATION, ISSN 0931-0509, Vol. 24, no 10, 3061-3067 p.Article in journal (Refereed) Published
Abstract [en]

Background. There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis. Methods. We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephropathy patients, 146 men and 66 women and 477 healthy age-matched controls (321 men and 156 women) from the same population in Sweden. Results. Frequencies of four out of five selected SNPs (rs6957, rs2241715, rs1800471, rs1982073 and rs1800469) were found to significantly differ between male patients and male controls in a co-dominant model (corrected P andlt;= 0.05) and of two SNPs (rs1982073 and rs1800469) in the allelic model (P andlt;= 0.05 in 100 000 permutation test). Haplotype analysis for five selected SNPs revealed a significant association of TGGCG with protective effect (P = 0.0012, empirical P = 0.006, 100 000 permutations) and of CT-GTA with susceptibility effect (P = 0.0018, empirical P = 0.008, 100 000 permutations). In our study, no association with TGFB1 variations was found when comparing female patients and female controls. No association was found for TGFB1 markers with disease progression for selected individuals from the patients group. In addition, meta-analysis performed for SNP rs1982073 for combined patients and controls from our study together with published data from two independent studies showed a significant association. Conclusions. Our experimental data together with the meta-analysis suggest TGFB1 as an important candidate gene for further biological studies of IgA nephropathy and as a possible target for therapy. Our data also indicate a possibility of a gender effect in the genetic background of IgA nephropathy.

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2009. Vol. 24, no 10, 3061-3067 p.
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Medical and Health Sciences
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URN: urn:nbn:se:liu:diva-51277DOI: 10.1093/ndt/gfp079OAI: oai:DiVA.org:liu-51277DiVA: diva2:273922
Available from: 2009-10-26 Created: 2009-10-26 Last updated: 2014-10-01

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Fernström, Anders

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NephrologyFaculty of Health SciencesDepartment of Nephrology UHL
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