Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy in African Americans.
Variants in the engulfment and cell motility 1 (ELMO1) gene are associated with nephropathy due to type 2 diabetes mellitus (T2DM) in a Japanese cohort. We comprehensively evaluated this gene in African American (AA) T2DM patients with end-stage renal disease (ESRD). Three hundred and nine HapMap tagging SNPs and 9 reportedly associated SNPs were genotyped in 577 AA T2DM-ESRD patients and 596 AA non-diabetic controls, plus 43 non-diabetic European American controls and 45 Yoruba Nigerian samples for admixture adjustment. Replication analyses were conducted in 558 AA with T2DM-ESRD and 564 controls without diabetes. Extension analyses included 328 AA with T2DM lacking nephropathy and 326 with non-diabetic ESRD. The original and replication analyses confirmed association with four SNPs in intron 13 (permutation p-values for combined analyses = 0.001-0.003), one in intron 1 (P = 0.004) and one in intron 5 (P = 0.002) with T2DM-associated ESRD. In a subsequent combined analysis of all 1,135 T2DM-ESRD cases and 1,160 controls, an additional 7 intron 13 SNPs produced evidence of association (P = 3.5 x 10(-5)- P = 0.05). No associations were seen with these SNPs in those with T2DM lacking nephropathy or with ESRD due to non-diabetic causes. Variants in intron 13 of the ELMO1 gene appear to confer risk for diabetic nephropathy in AA.
Leak
T S
TS
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Perlegas
P S
PS
Smith
S G
SG
Keene
K L
KL
Hicks
P J
PJ
Langefeld
C D
CD
Mychaleckyj
J C
JC
Rich
S S
SS
Kirk
J K
JK
Freedman
B I
BI
Bowden
D W
DW
Sale
M M
MM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D048868:Adaptor Proteins, Signal Transducing; C465214:ELMO1 protein, human