Polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) are associated with the progression of IgA nephropathy in Chinese

Abstract

IgA nephropathy (IgAN) is the leading cause of end-stage renal disease (ESRD) in China considering different compositions of ESRD causes in different ethnicities. A recent genome-wide association study (GWAS) indicated that the MYH9 gene was significantly associated with non-diabetic ESRD in African-Americans and also influenced kidney function in Europeans. Thus, in the present study, we aim to clarify whether MYH9 confers a shared mechanism among different causes of ESRD and to seek possible further insight into our understanding of IgAN by applying GWAS data from ESRD to IgAN. One thousand one hundred and sixteen Chinese, including 527 patients with renal biopsy-proven IgAN and 589 healthy controls, were enrolled in the present study. Four single neucleotide polymorphisms (SNPs) (rs3752462, rs4821480, rs11089788 and rs2413396) reported to be associated with ESRD with the most significance were genotyped by TaqMan assay or a restriction fragment length polymorphism assay for a further case-control study. None of the four SNPs was associated with the susceptibility to IgAN or clinical and pathological characters at the time of renal biopsy. However, estimated glomerular filtration rate decline rate was associated with rs11089788 in the dominant model (P = 0.021). Cox regression showed that rs11089788 (hazard ratio, 3.95; 95% confidence interval, 1.23-12.63; P = 2.1 × 10(-2)) was an independent predictive factor for renal survival. Based on a large Chinese IgAN cohort, we found an association between rs11089788 and prognosis of IgAN, adding to the mounting evidence of MYH9 as an important gene in IgAN to ESRD.