Confirmation of genetic associations at ELMO1 in the GoKinD collection supports its role as a susceptibility gene in diabetic nephropathy.
OBJECTIVE
To examine the association between single nucleotide polymorphisms (SNPs) in the engulfment and cell motility 1 (ELMO1) gene, a locus previously shown to be associated with diabetic nephropathy in two ethnically distinct type 2 diabetic populations, and the risk of nephropathy in type 1 diabetes.


METHODS
Genotypic data from a genome-wide association scan (GWAS) of the Genetics of Kidneys in Diabetes (GoKinD) study collection were analyzed for associations across the ELMO1 locus. In total, genetic associations were assessed using 118 SNPs and 1,705 individuals of European ancestry with type 1 diabetes (885 normoalbuminuric control subjects and 820 advanced diabetic nephropathy case subjects).


RESULTS
The strongest associations in ELMO1 occurred at rs11769038 (odds ratio [OR] 1.24; P = 1.7 x 10(-3)) and rs1882080 (OR 1.23; P = 3.2 x 10(-3)) located in intron 16. Two additional SNPs, located in introns 18 and 20, respectively, were also associated with diabetic nephropathy. No evidence of association for variants previously reported in type 2 diabetes was observed in our collection.


CONCLUSIONS
Using GWAS data from the GoKinD collection, we comprehensively examined evidence of association across the ELMO1 locus. Our investigation marks the third report of associations in ELMO1 with diabetic nephropathy, further establishing its role in the susceptibility of this disease. There is evidence of allelic heterogeneity, contributed by the diverse genetic backgrounds of the different ethnic groups examined. Further investigation of SNPs at this locus is necessary to fully understand the commonality of these associations and the mechanism(s) underlying their role in diabetic nephropathy.
Pezzolesi
Marcus G
MG
Research Division, Joslin Diabetes Center, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Katavetin
Pisut
P
Kure
Masahiko
M
Poznik
G David
GD
Skupien
Jan
J
Mychaleckyj
Josyf C
JC
Rich
Stephen S
SS
Warram
James H
JH
Krolewski
Andrzej S
AS
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001794:Blood Pressure; D002465:Cell Movement; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D044465:White People / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D006442:Glycated Hemoglobin; C465214:ELMO1 protein, human