Introduction: IgA nephritis (IgAN) is the most common glomerulonephritis worldwide. We aim to genotype SNPs (single nucleotide polymorphisms) genomewide in patients with IgAN to search for genetic clues to its aetiology. Materials and Methods: Genotyping for 10,204 SNPs genomewide was done with the Gene Chip Human Mapping 10K Microarray (Affymetrix). Twenty-eight patients with IgAN and 30 normal subjects were screened and analysed for differences in genotype frequency, allele frequency and heterozygosity reduction. Results: Among the most significantly associated SNPs, 48 SNPs were found mapping directly to the intron of 42 genes that localised in 13 somatic chromosomes and chromosome X. Genotype distribution of these SNPs did not deviate from the Hardy-Weinberg equilibrium in normal subjects. The most significantly associated gene, glial cells missing homolog 1 (GCM, 2 =13.05, P = 0.000) is a transcription factor mapped to 6p12.2. GCM1 reported decreased in placenta of patients with pre-eclampsia. The second gene, Tenascin-R (TNR, 2 = 9.85, P = 0.002) is a glycoprotein and extra-cellular matrix component mapped to 1q25.1. Tenascin-R was associated with motor coordination impairment and enhanced anxiety profile in deficient mice. Interestingly, Triadin (TRDN, 2 = 9.16, P = 0.01) is an integral membrane protein mapped to 6q22.31 within the IgAN1 locus. Triadin was shown to participate in cardiac myocyte arrhythemia. However, there is no published study of these genes in IgAN. Conclusion: Forty-two associated genes (particularly GCM1, TNR and TRDN) are identified as possible susceptibility or marker genes for IgAN. Knowledge of their mesangial expression and binding capacity for IgA-containing complexes may help elucidate the pathogenesis of IgAN.
Worldwide, IgA nephropathy (IgAN) is now recognised as the most common form of primary glomerulonephritis.1,2 It is an important cause of chronic kidney disease and up to 30% to 40% of patients progress to end-stage renal failure within 20 years after diagnosis.3 Its causes remain unknown and treatment is symptomatic.4 The lesion is characterised by the predominant deposition of IgA in the mesangium and para-mesangial regions. These deposits may be immune-complexes with a wide range of antigens. They may be aggregates of abnormal IgA1 with aberrant galactosylation in the hinged-region.5 Such depositions conceivably activated the renal cells to express various cytokines and growth factors.6 The results are mesangial cell proliferation and expansion of the mesangial matrix, both characteristic histological features of the disease. Damage to the glomerular structure can lead to leakage of serum proteins and red blood cells giving rise to proteinuria and haematuria which are frequently observed in the urine of patients with IgAN. The proteinuria, if heavy and left unchecked, will lead to further damage in the tubules and progression to end-stage renal failure.7,8
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