RGD Reference Report - Non-muscle myosin heavy chain 9 gene MYH9 associations in African Americans with clinically diagnosed type 2 diabetes mellitus-associated ESRD. - Rat Genome Database

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Non-muscle myosin heavy chain 9 gene MYH9 associations in African Americans with clinically diagnosed type 2 diabetes mellitus-associated ESRD.

Authors: Freedman, BI  Hicks, PJ  Bostrom, MA  Comeau, ME  Divers, J  Bleyer, AJ  Kopp, JB  Winkler, CA  Nelson, GW  Langefeld, CD  Bowden, DW 
Citation: Freedman BI, etal., Nephrol Dial Transplant. 2009 Nov;24(11):3366-71. Epub 2009 Jun 30.
RGD ID: 6903238
Pubmed: PMID:19567477   (View Abstract at PubMed)
PMCID: PMC2910323   (View Article at PubMed Central)
DOI: DOI:10.1093/ndt/gfp316   (Journal Full-text)

BACKGROUND: Although MYH9 is strongly associated with biopsy-proven idiopathic and HIV-associated focal segmental glomerulosclerosis (FSGS) and clinically diagnosed 'hypertension-associated' end-stage renal disease (ESRD) in African Americans, its role in type 2 diabetes mellitus (T2DM)-associated ESRD is unclear. METHODS: To assess whether MYH9 was associated with T2DM-ESRD, 751 African Americans with T2DM-ESRD, 227 with T2DM lacking nephropathy and 925 non-diabetic non-nephropathy controls were genotyped for 14 MYH9 SNPs. Association analyses used SNPGWA and Dandelion. RESULTS: Comparing T2DM-ESRD cases with non-diabetic controls, single SNP associations were detected with 8 of 14 SNPs, gender- and admixture-adjusted P-values 0.047-0.005 [recessive model, odds ratio (OR) range 1.30-1.55]. The previously associated MYH9 E1 and L1 haplotypes were associated with T2DM-ESRD (E1: OR 1.27, 95% CI 1.04-1.56, P = 0.021 recessive and L1: OR 1.43, 95% CI 1.09-1.87, P = 0.009 dominant). Contrasting the 751 T2DM-ESRD cases with 227 T2DM non-nephropathy controls revealed that E1 haplotype SNPs rs4821480, rs2032487 and rs4821481 were associated with kidney failure (OR 1.38-1.40 recessive, all P < 0.048). Among E1 and L1 risk homozygotes, respectively, mean (SD) diabetes duration prior to renal replacement therapy was 16.6 (9.7) and 16.4 (10.0) years, and 65% had diabetic retinopathy. CONCLUSIONS: Genetic dissection of T2DM-associated ESRD reveals that MYH9 underlies a portion of this clinically diagnosed disorder in African Americans. It is likely that a subset of African Americans with T2DM and coincident nephropathy have primary MYH9-related kidney disease (e.g. FSGS or global glomerulosclerosis), although renal biopsy studies need to be performed.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
end stage renal disease  IAGP 6903238associated with diabetes mellitus more ...RGD 
end stage renal disease  ISOMYH9 (Homo sapiens)6903238; 6903238associated with diabetes mellitus more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myh9  (myosin, heavy chain 9)

Genes (Mus musculus)
Myh9  (myosin, heavy polypeptide 9, non-muscle)

Genes (Homo sapiens)
MYH9  (myosin heavy chain 9)


Additional Information