Variants in Intron 13 of the ELMO1 Gene are Associated with Diabetic Nephropathy in African Americans

Abstract

SummaryVariants 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 × 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.

Integrating Human and Rodent Data to Identify the Genetic Factors Involved in Chronic Kidney Disease

“…22 Variants at this locus have since been reported in two large African-American cohorts with type 2 diabetes and ESRD and in a collection of Caucasian type 1 diabetic patients from the Genetics of Kidneys in Diabetes (GoKinD) study. 25,26 Interestingly, this same region has also been linked with ESRD and variation in GFR. 27,28 A second GWA study in Pima Indians with type 2 diabetes identified a strong association in intron 8 of the plasmacytoma variant translocation (PVT1) gene.…”

High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy

“…In a genome-wide case control association study in Japan, over 80,000 single-nucleotide polymorphism (SNP) loci were tested and one SNP locus in the 18th intron of the ELMO1 gene was found to be strongly associated with nephropathy due to type 2 diabetes (χ 2 = 19.9; P = 0.000008; odds ratio, 2.7) (5). Later studies have demonstrated an association of SNPs in the ELMO1 gene and the susceptibility to type 1 diabetic nephropathy in Caucasians (6,7), Pima Indians (8), African Americans (9), and Chinese population (10), although some other studies have reported that the association is not significant (11,12).…”

Examination of Association with Candidate Genes for Diabetic Nephropathy in a Mexican American Population

“…We attempt to replicate the previous associations of CNDP1 and ELMO1 with a sample size that is similar or greater than previously used (2)(3)(4)(5). In addition, we study the following eight genes, which are good biologic candidates but have not been studied extensively: hemicentin 1 (HMCN1), complement factor H (CFH), ␣-2-Heremans-Schmid-glycoprotein (AHSG), caspase 3 (CASP3), heat shock 70-kD protein 1A (HSPA1A), heat shock 27-kD protein 1 (HSPB1), caspase 12 (CASP12), and heme oxygenase (decycling) 1 (HMOX1).…”