Association of the Distal Region of the Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Gene With Type 2 Diabetes in an African-American Population Enriched for Nephropathy

Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Diabetes (Impact Factor: 8.1). 04/2008; 57(4):1057-62. DOI: 10.2337/db07-0886
Source: PubMed


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).
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 chi(2) statistic and corresponding P value.
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.
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.

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Available from: Tennille Leak-Johnson, Nov 27, 2015
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    • "African American association with T2DM-ESRD Genotypic association results for 208 SNPs from eight T2DM candidate genes: two Calpain 10 (CAPN10) SNPs, one Peroxisome proliferator–activated receptor γ (PPARG) SNP, five Transcription factor 7-like 2 (TCF7L2) SNPs, one ATP-sensitive inwardly rectifying potassium channel subunit Kir6.2 (KCNJ11) SNP, one Hepatic transcription factor 1 (TCF1) SNP, three Hepatocyte nuclear factor 4-α (HNF4A) SNPs (Sale et al. 2007), 146 Estrogen receptor α gene (ESR1) SNPs (Keene et al 2008b) and 49 Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) SNPs, (Keene et al 2008a "
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