title: Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy in African Americans.
abstract: 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.
authors.affiliation: Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Leak
authors.forename: P S
authors.initials: PS
authors.lastname: Perlegas
authors.forename: S G
authors.initials: SG
authors.lastname: Smith
authors.forename: K L
authors.initials: KL
authors.lastname: Keene
authors.forename: P J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: C D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: J C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: S S
authors.initials: SS
authors.lastname: Rich
authors.forename: J K
authors.initials: JK
authors.lastname: Kirk
authors.forename: B I
authors.initials: BI
authors.lastname: Freedman
authors.forename: D W
authors.initials: DW
authors.lastname: Bowden
authors.forename: M M
authors.initials: MM
authors.lastname: Sale
mesh_terms: 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
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C465214:ELMO1 protein, human