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- Title
Association of the Distal Region of the Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Gene With Type 2 Diabetes in an African-American Population Enriched for Nephropathy.
- Authors
Keene, Keith L.; Mychaleckyj, Josyf C.; Smith, Shelly G.; Leak, Tennille S.; Perlegas, Peter S.; Langefeld, Carl D.; Freedman, Barry I.; Rich, Stephen S.; Bowden, Donald W.; Sale, Michèle M.
- Abstract
OBJECTIVE--Variants in the ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1) gene have shown positive associations with diabetes and related phenotypes, including insulin resistance, metabolic syndrome, and type 1 diabetic nephropathy. Additionally, evidence for linkage for type 2 diabetes in African Americans was observed at 6q24-27, with the proximal edge of the peak encompassing the ENPP1 gene. Our objective was to comprehensively evaluate variants in ENPP1 for association with type 2 diabetic end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS--Forty-nine single nucleotide polymorphisms (SNPs) located in the coding and flanking regions of ENPP1 were genotyped in 577 African-American individuals with type 2 diabetic ESRD and 596 African-American control subjects. Haplotypic association and genotypic association for the dominant, additive, and recessive models were tested by calculating a χ² statistic and corresponding P value. RESULTS--Nine SNPs showed nominal evidence for association (P < 0.05) with type 2 diabetic ESRD in one or more genotypic model. The most significant associations were observed with rs7754586 (P = 0.003 dominant model, P = 0.0005 additive, and P = 0.007 recessive), located in the 3′ untranslated region, and an intron 24 SNP (rs1974201: P = 0.004 dominant, P = 0.0005 additive, and P = 0.005 recessive). However, the extensively studied K121Q variant (rs1044498) did not reveal evidence for association with type 2 diabetic ESRD in this African-American population. CONCLUSIONS--This study was the first to comprehensively evaluate variants of the ENPP1 gene for association in an African-American population with type 2 diabetes and ESRD and suggests that variants in the distal region of the ENPP1 gene may contribute to diabetes or diabetic nephropathy susceptibility in African Americans.
- Subjects
GENES; PYROPHOSPHATES; PHOSPHODIESTERASES; NUCLEOTIDES; AFRICAN Americans; KIDNEY diseases
- Publication
Diabetes, 2008, Vol 57, Issue 4, p1057
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db07-0886