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  • Title: Replication of genome-wide association study identified seven susceptibility genes, affirming the effect of rs2856717 on renal function and poor outcome of IgA nephropathy.
    Author: Wang W, Li G, Hong D, Zou Y, Fei D, Wang L.
    Journal: Nephrology (Carlton); 2017 Oct; 22(10):811-817. PubMed ID: 27450519.
    Abstract:
    AIM: Meta-analysis of data from a genome-wide association study (GWAS) identified seven single nucleotide polymorphisms (SNPs) as strong predictors of IgA nephropathy (IgAN). To replicate the association of these seven SNPs and understand whether they influence the clinical characteristics of IgAN, a case-control study including 521 IgAN patients and 535 controls was conducted in a Western Han cohort. METHODS: Data were analyzed using logistic regression and multifactor dimensionality reduction (MDR). Clinical data collected from 459 IgAN patients were investigated to estimate the relationship between the genotype and phenotype of IgAN. A retrospective cohort study of 315 IgAN patients was conducted to investigate the relationship between genotype and progression of renal disease over a mean period of 44.49 ± 19.94 months. RESULTS: Upon Bonferroni correction, none of the seven SNPs were associated with IgAN (corrected P-value [Pc], >0.05). A combination of the rs2856717T/C, rs9275596C/T, and rs2412971A/G had effects on the susceptibility of IgAN (P = 0.001). Marginally significant association of rs2856717 T/C recessive model for the T allele was significantly associated with estimated glomerular filtration rate (eGFR) (<60 mL/min per 1.73 m2 ) in IgAN patients (P = 0.008, Pc = 0.056, odds ratio [OR] = 1.527). The T allele at rs9275596 was significantly associated with macroscopic haematuria of IgAN patients under the dominant and additive models of inheritance, (P < 0.001, Pc = 0.007, OR = 2.983) and (P < 0.001, Pc = 0.007, OR = 2.17), respectively. Kaplan-Meier survival analysis showed that patients carrying the TT + TC genotype for rs2856717 had reduced renal survival rate than those carrying the CC genotype (85.1% vs. 92.7%, P = 0.046). CONCLUSION: rs2856717 may influence the clinical characteristics and poor outcome of IgAN. Further studies are warranted to explore the mechanisms for such genotype-disease phenotype association.
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