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.
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).
  
  
  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 chi(2) 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.
authors.affiliation: Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Keene
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Shelly G
authors.initials: SG
authors.lastname: Smith
authors.forename: Tennille S
authors.initials: TS
authors.lastname: Leak
authors.forename: Peter S
authors.initials: PS
authors.lastname: Perlegas
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
mesh_terms: D017668:Age of Onset; D000368:Aged; D044383:Black People / Q000235:genetics*; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D012016:Reference Values; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases