NDT Advance Access originally published online on January 23, 2006
Nephrology Dialysis Transplantation 2006 21(6):1570-1574; doi:10.1093/ndt/gfk096
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Association of MEGSIN 2093C–2180T haplotype at the 3' untranslated region with disease severity and progression of IgA nephropathy
1 Department of Nephrology, First Affiliated Hospital, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, 2 Department of Nephrology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 3 Department of Medical Statistics, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, PR China, 4 Department of Medicine, Queen Marry Hospital, The University of Hong Kong, Hong Kong, 5 Department of Medical Genetics, Zhongshan Medical College, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou, PR China and 6 Renal Section, Hammersmith Hospital, Imperial College, Du Cane Road, London W12 0NN, UK
Correspondence and offprint requests to: Prof. Yiming Wang, Department of Medical Genetics, Zhongshan Medical College, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou 510089, PR China. Email: ywzhong{at}hotmail.com
Background. MEGSIN is a gene predominantly expressed in the renal mesangium, and is upregulated in IgA nephropathy (IgAN). Our previous study has shown that the 2093C and 2180T alleles at the 3' untranslated region (3'UTR) of the gene are associated with susceptibility to IgAN, but the relationships of these genetic variants with the clinical manifestations and renal histological lesions of IgAN have not been examined previously.
Methods. 302 IgAN patients followed up for 52.8±22.5 months were investigated. Haplotypes at the 3'UTR were constructed using the 2093C/T and 2180C/T alleles. The genotype–phenotype relationship was studied by correlations of haplotypes and the clinical data and renal histopathological changes.
Results. The 2093C–2180T haplotype was present more often in patients with disease that progressed more rapidly (
2(C-T/others) = 8.429, P = 0.004), and was also correlated with hypertension (2(C-T/others) = 6.459, P = 0.012), severe proteinuria (
2 g/d) (2(C-T/others) = 6.332, P = 0.013), and Lee's class IV and V histological changes (2(C-T/others) = 9.640, P = 0.008).
Conclusion. In this Chinese population, the 2093C–2180T haplotype at the 3'UTR of MEGSIN gene is associated with more severe forms of IgAN, and more rapid disease progression. This provides further evidence for the involvement of genetic variations of MEGSIN in the pathogenesis of IgAN.
Keywords: Chinese; genetic variations; genotype–phenotype relationship; IgAN; MEGSIN
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