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Background. IgA nephropathy is a major cause of end-stage renal disease worldwide. Its aetiology is poorly understood but there is good evidence for a major genetic component, although to date, no gene has been conclusively identified. We describe a new UK multicentre DNA collection assembled to investigate this. A Japanese genome-wide analysis recently reported that common genetic variation in immunoglobulin mu-binding protein 2 (IGHMBP2) was associated with IgA nephropathy. We sought to replicate this using the new UK collection, and through an independent parallel analysis of a Han Chinese population. [ABSTRACT FROM PUBLISHER]

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 (χ2(C-T/others) = 8.429, P = 0.004), and was also correlated with hypertension (χ2(C-T/others) = 6.459, P = 0.012), severe proteinuria (≥2 g/d) (χ2(C-T/others) = 6.332, P = 0.013), and Lee's class IV and V histological changes (χ2(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. [ABSTRACT FROM AUTHOR]