PMID- 19567477
OWN - NLM
STAT- MEDLINE
DCOM- 20100107
LR  - 20221207
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 24
IP  - 11
DP  - 2009 Nov
TI  - Non-muscle myosin heavy chain 9 gene MYH9 associations in African Americans with 
      clinically diagnosed type 2 diabetes mellitus-associated ESRD.
PG  - 3366-71
LID - 10.1093/ndt/gfp316 [doi]
AB  - 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.
FAU - Freedman, Barry I
AU  - Freedman BI
AD  - 1Internal Medicine/Nephrology, 2Biochemistry, 3Biostatistical Sciences, Wake 
      Forest University School of Medicine, Winston-Salem, NC, USA. bfreedma@wfubmc.edu
FAU - Hicks, Pamela J
AU  - Hicks PJ
FAU - Bostrom, Meredith A
AU  - Bostrom MA
FAU - Comeau, Mary E
AU  - Comeau ME
FAU - Divers, Jasmin
AU  - Divers J
FAU - Bleyer, Anthony J
AU  - Bleyer AJ
FAU - Kopp, Jeffrey B
AU  - Kopp JB
FAU - Winkler, Cheryl A
AU  - Winkler CA
FAU - Nelson, George W
AU  - Nelson GW
FAU - Langefeld, Carl D
AU  - Langefeld CD
FAU - Bowden, Donald W
AU  - Bowden DW
LA  - eng
GR  - R01 HL055673-10/HL/NHLBI NIH HHS/United States
GR  - R01 DK070941/DK/NIDDK NIH HHS/United States
GR  - R01 DK53591/DK/NIDDK NIH HHS/United States
GR  - R01 DK053591-09/DK/NIDDK NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - N01 CO012400/CO/NCI NIH HHS/United States
GR  - R01 DK053591/DK/NIDDK NIH HHS/United States
GR  - R01 DK 070941/DK/NIDDK NIH HHS/United States
GR  - N01CO12400/CA/NCI NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - R01 HL055673/HL/NHLBI NIH HHS/United States
GR  - N01-CO-12400/CO/NCI NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20090630
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (MYH9 protein, human)
RN  - 0 (Molecular Motor Proteins)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
MH  - Adult
MH  - Black or African American/*genetics
MH  - Aged
MH  - Diabetes Mellitus, Type 2/*complications/ethnology
MH  - Diabetic Nephropathies/*genetics
MH  - Female
MH  - Humans
MH  - Kidney Failure, Chronic/ethnology/*genetics
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Molecular Motor Proteins/*genetics
MH  - Myosin Heavy Chains/*genetics
MH  - *Polymorphism, Single Nucleotide
PMC - PMC2910323
EDAT- 2009/07/02 09:00
MHDA- 2010/01/08 06:00
PMCR- 2010/11/01
CRDT- 2009/07/02 09:00
PHST- 2009/07/02 09:00 [entrez]
PHST- 2009/07/02 09:00 [pubmed]
PHST- 2010/01/08 06:00 [medline]
PHST- 2010/11/01 00:00 [pmc-release]
AID - gfp316 [pii]
AID - 10.1093/ndt/gfp316 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2009 Nov;24(11):3366-71. doi: 10.1093/ndt/gfp316. Epub 
      2009 Jun 30.