MYH9-RD is characterized by a considerable variability in clinical evolution: patients present at birth with only thrombocytopenia, but some of them subsequently develop sensorineural deafness, cataract, and/or nephropathy often leading to end-stage renal disease (ESRD).
Since APOL1 is strongly associated with ESRD in African Americans, interactions between APOL1 and MYH9 risk variants and hemoglobin S were assessed using case-only and case-control centered two-way logistic regression interaction analyses.
The myosin, heavy chain 9, non-muscle (MYH9) and apolipoprotein L1 (APOL1) genes have been associated with risk for focal segmental glomerulosclerosis and end-stage renal disease in African Americans.
Admixture mapping recently identified the nonmuscle myosin heavy chain 9 gene (MYH9) as a susceptibility factor strongly associated with several nondiabetic etiologies of end-stage renal disease in African Americans, less strongly with diabetes-associated end-stage renal disease.
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.
These findings strengthen the contention that a sequence variant of MYH9, common in populations with varying degrees of African ancestry admixture, and in strong linkage disequilibrium with the associated SNPs and haplotypes reported herein, strongly predisposes to non-diabetic ESKD.
The spectrum of MYH9-associated kidney disease, including focal segmental glomerulosclerosis, global glomerulosclerosis and collapsing glomerulopathy, related entities contributing to approximately 43% of end-stage renal disease in African-Americans, has come to light.
Dense mapping of MYH9 identified individual single nucleotide polymorphisms (SNPs) and sets of such SNPs grouped as haplotypes that were found to be highly associated with a large and important group of ESKD risk phenotypes, which as a consequence were designated as MYH9-associated nephropathies (Bostrom and Freedman 2010).
The contribution of variants in this single MYH9 gene to ethnic differences in the incidence rates of end-stage renal disease is now clearly established.
Admixture mapping recently identified MYH9 as a susceptibility gene for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy (HIVAN) and end-stage kidney disease attributed to hypertension (H-ESKD) in African Americans (AA).
Thus, hypertension-associated ESRD in African Americans is substantially related to MYH9 gene polymorphisms and this may explain the poor response to blood pressure control in those diagnosed with hypertensive nephrosclerosis.
Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.
Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.