Complement factor H gene polymorphism rs6677604 and the risk, severity and progression of IgA nephropathy: A systematic review and meta‐analysis

• Published in: Nephrology (Carlton, Vic.) Vol. 23; no. 12; pp. 1096 - 1106
• Main Authors: Yeo, See Cheng, Liu, Xinyang, Liew, Adrian
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01.12.2018; Wiley Subscription Services, Inc
• Subjects: Adult; Alleles; Complement activation; Complement factor H; Complement Factor H - genetics; Complement Factor H - immunology; Disease Progression; Female; Gene Frequency; Gene polymorphism; Genetic Predisposition to Disease; Genotype & phenotype; Glomerulonephritis, IGA - diagnosis; Glomerulonephritis, IGA - ethnology; Glomerulonephritis, IGA - genetics; Glomerulonephritis, IGA - immunology; H gene; Humans; IgA nephropathy; Immunoglobulin A; Male; Meta-analysis; Middle Aged; Minority & ethnic groups; Phenotype; Polymorphism; Polymorphism, Single Nucleotide; Protective Factors; Risk Assessment; Risk Factors; rs6677604; Severity of Illness Index; Systematic review; meta-analysis; IgA nephropathy; complement factor H; rs6677604
• ISSN: 1320-5358; 1440-1797; 1440-1797
• DOI: 10.1111/nep.13210

ABSTRACT Aim Studies reporting the association between complement factor H gene rs6677604 polymorphism and susceptibility to IgA nephropathy (IgAN) had yielded inconsistent results. We performed a systematic review and meta‐analysis to clarify the association between rs6677604 and IgAN susceptibility, disease severity and chronic progression. Methods A comprehensive database search was performed to identify eligible studies. Meta‐analyses were performed for rs6677604 allele frequency, genotypes and the association with IgAN susceptibility. Results 10 studies were included in the systematic review. Among them, four studies containing 10 distinct datasets (15,617 cases and 31,957 controls) were included in the meta‐analysis. The pooled frequency of the minor allele (A) was significantly higher in Europeans than in Asians across both IgAN cases and controls, and the frequency of the minor allele (A) in IgAN cases was also significantly lower than that in controls across both European and Asian subgroups. Significant associations were detected between rs6677604 and risk of developing IgAN, when comparing allele A vs. G, genotype AA vs. GG, genotype AA vs. AG and genotype AG vs. GG. In analysis stratified by ethnicity, significant association was only observed in Europeans but not in Asians when comparing AA vs. GG or AA vs. AG. Conclusion Our pooled analysis showed a significant association between rs6677604‐(A) allele and IgAN susceptibility, supporting the importance of complement activation in the pathogenesis of IgAN. The presence of rs6677604‐(A) allele may be associated with a decreased the risk of IgAN in Europeans, but the association was not confirmed in Asians. Summary at a Glance This paper is a meta‐analysis and systematic review of the role of rs6677604 in IgAN using published studies and reinforces the importance of complement regulation in the pathogenesis of IgAN