Aims: To investigate the association of megsin A23167G polymorphism with susceptibility and progression of IgA nephropathy in Chinese population.
Methods: 435 IgA nephropathy patients and their family members were recruited for a family-based association study. Genotypes of megsin A23167G were determined by direct sequencing. The results were analyzed by transmission disequilibrium test (TDT) and haplotype relative risk (HRR). Clinical data and histological scores of renal lesions were compared between patients with different genotypes. According to disease stability, IgA nephropathy patients were divided into progressive group and stable group. The distribution of genotype frequencies were compared between the 2 groups.
Results: TDT revealed that megsin 23167G alleles were transmitted more frequently from heterozygous parents to patients than expected (classical TDT: chi2 = 5.435, p = 0.020, extended TDT: chi2 = 5.017, p = 0.025). HRR analyses showed significant differences between transmitted and nontransmitted allele frequencies (chi2 = 7.006, p = 0.008, HRR = 1.762). The scores of glomerular index and glomerular sclerosis index were higher in GG genotype patients than those in other genotypes (F = 4.570, p = 0.033, F = 4.324, p = 0.038, respectively). The distribution frequency of GG genotype in the progressive group was higher than that of the stable group (chi2 = 4.370, p = 0.037). No statistical difference was found in tubulo-interstitial index, vascular index and clinical characteristics between the 2 groups.
Conclusion: The polymorphism of megsin A23167G is associated with susceptibility and progression of IgA nephropathy in Chinese population. GG genotype is associated with severe histological lesions and progression of the disease.