ELMO1 variants and susceptibility to diabetic nephropathy in American Indians.
Variants in the engulfment and cell motility 1 gene, ELMO1, have previously been associated with kidney disease attributed to type 2 diabetes. The Pima Indians of Arizona have high rates of diabetic nephropathy, which is strongly dependent on genetic determinants; thus, we sought to investigate the role of ELMO1 polymorphisms in mediating susceptibility to this disease in this population. Genotype distributions were compared among 141 individuals with nephropathy and 416 individuals without heavy proteinuria in a family study of 257 sibships, and 107 cases with diabetic ESRD and 108 controls with long duration diabetes and no nephropathy. We sequenced 17.4 kb of ELMO1 and identified 19 variants. We genotyped 12 markers, excluding those in 100% genotypic concordance with other variants or with a minor allele frequency <0.05, plus 21 additional markers showing association with ESRD in earlier studies. In the family study, the strongest evidence for association was with rs1345365 (odds ratio [OR]=2.42 per copy of A allele [1.35-4.32]; P=0.001) and rs10951509 (OR=2.42 per copy of A allele [1.31-4.48]; P=0.002), both of which are located in intron 13 and are in strong pairwise linkage disequilibrium (r(2)=0.97). These associations were in the opposite direction from those observed in African Americans, which suggests that the relationship between diabetic kidney disease and ELMO1 variation may involve as yet undiscovered functional variants or complex interactions with other biological variables.
Hanson
Robert L
RL
Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 1550 East Indian School Road, Phoenix, AZ 85014, USA.
Millis
Meredith P
MP
Young
Naomi J
NJ
Kobes
Sayuko
S
Nelson
Robert G
RG
Knowler
William C
WC
DiStefano
Johanna K
JK
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D048868:Adaptor Proteins, Signal Transducing; C465214:ELMO1 protein, human
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