The non-muscle Myosin heavy chain 9 gene (MYH9) is not associated with lupus nephritis in African Americans.
BACKGROUND
African Americans (AA) disproportionately develop lupus nephritis (LN) relative to European Americans and familial clustering supports causative genes. Since MYH9 underlies approximately 40% of end-stage renal disease (ESRD) in AA, we tested for genetic association with LN.


METHODS
Seven MYH9 single nucleotide polymorphisms (SNPs) and the E1 risk haplotype were tested for association with LN in three cohorts of AA.


RESULTS
A preliminary analysis revealed that the MYH9 E1 risk haplotype was associated with ESRD in 25 cases with presumed systemic lupus erythematosus (SLE)-associated ESRD, compared to 735 non-SLE controls (odds ratio 3.1; p = 0.010 recessive). Replication analyses were performed in 583 AA with SLE in the PROFILE cohort (318 with LN; 265 with SLE but without nephropathy) and 60 AA from the NIH (39 with LN; 21 with SLE but without nephropathy). Analysis of the NIH and larger PROFILE cohorts, as well as a combined analysis, did not support this association.


CONCLUSIONS
These results suggest that AA with ESRD and coincident SLE who were recruited from dialysis clinics more likely have kidney diseases in the MYH9-associated spectrum of focal segmental glomerulosclerosis. PROFILE and NIH participants, recruited from rheumatology practices, demonstrate that MYH9 does not contribute substantially to the development of LN in AA.
Freedman
Barry I
BI
Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1053, USA. bfreedma@wfubmc.edu
Edberg
Jeffrey C
JC
Comeau
Mary E
ME
Murea
Mariana
M
Bowden
Donald W
DW
Divers
Jasmin
J
Alarcón
Graciela S
GS
Brown
Elizabeth E
EE
McGwin
Gerald
G
Kopp
Jeffrey B
JB
Winkler
Cheryl A
CA
Nelson
George W
GW
Illei
Gabor
G
Petri
Michelle
M
Ramsey-Goldman
Rosalind
R
Reveille
John D
JD
Vilá
Luis M
LM
Langefeld
Carl D
CD
Kimberly
Robert P
RP
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics* / Q000706:statistics & numerical data*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006239:Haplotypes; D006801:Humans; D008181:Lupus Nephritis / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult
C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains