Variants in Intron 13 of theELMO1Gene are Associated with Diabetic Nephropathy in African Americans
| Autor: | Pamela J. Hicks, Carl D. Langefeld, Peter S. Perlegas, Michèle M. Sale, B. I. Freedman, Josyf C. Mychaleckyj, Donald W. Bowden, Keith L. Keene, Shelly G. Smith, Tennille S. Leak, S. S. Rich, Julienne K. Kirk |
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| Rok vydání: | 2009 |
| Předmět: |
Male
endocrine system diseases Single-nucleotide polymorphism Type 2 diabetes Biology Polymorphism Single Nucleotide Article Nephropathy Diabetic nephropathy Diabetes mellitus Genetics medicine Humans Diabetic Nephropathies Genetic Predisposition to Disease International HapMap Project Genetics (clinical) Adaptor Proteins Signal Transducing Aged Intron nutritional and metabolic diseases Middle Aged medicine.disease Introns Black or African American ELMO1 Diabetes Mellitus Type 2 Female |
| Zdroj: | Annals of Human Genetics. 73:152-159 |
| ISSN: | 1469-1809 0003-4800 |
| Popis: | Summary 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 × 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. |
| Databáze: | OpenAIRE |
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