title: Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity.
abstract: The common missense single nucleotide polymorphism (SNP) K121Q in the ectoenzyme nucleotide pyrophosphate phosphodiesterase (ENPP1) gene has recently been associated with type 2 diabetes in Italian, U.S., and South-Asian populations. A three-SNP haplotype, including K121Q, has also been associated with obesity and type 2 diabetes in French and Austrian populations. We set out to confirm these findings in several large samples. We genotyped the haplotype K121Q (rs1044498), rs1799774, and rs7754561 in 8,676 individuals of European ancestry with and without type 2 diabetes, in 1,900 obese and 930 lean individuals of European ancestry from the U.S. and Poland, and in 1,101 African-American individuals. Neither the K121Q missense polymorphism nor the putative risk haplotype were significantly associated with type 2 diabetes or BMI. Two SNPs showed suggestive evidence of association in a meta-analysis of our European ancestry samples. These SNPs were rs7754561 with type 2 diabetes (odds ratio for the G-allele, 0.85 [95% CI 0.78-0.92], P = 0.00003) and rs1799774 with BMI (homozygotes of the delT-allele, 0.6 [0.42-0.88], P = 0.007). However, these findings are not supported by other studies. We did not observe a reproducible association between these three ENPP1 variants and BMI or type 2 diabetes.
authors.affiliation: Division of Genetics, Children's Hospital Boston, Enders 561, 300 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Helen N
authors.initials: HN
authors.lastname: Lyon
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Todd
authors.initials: T
authors.lastname: Bersaglieri
authors.forename: Richa
authors.initials: R
authors.lastname: Saxena
authors.forename: Wendy
authors.initials: W
authors.lastname: Winckler
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Ulf
authors.initials: U
authors.lastname: Lindblad
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.forename: Richard
authors.initials: R
authors.lastname: Cooper
authors.forename: Kristin G
authors.initials: KG
authors.lastname: Ardlie
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D003920:Diabetes Mellitus / Q000201:enzymology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009765:Obesity / Q000201:enzymology / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D015203:Reproducibility of Results; D035781:Siblings; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases