title: Ethnic differences in the frequency of ENPP1/PC1 121Q genetic variant in the Dallas Heart Study cohort.
abstract: Genetic susceptibility modulates the impact of obesity on the risk for type 2 diabetes. One candidate gene predisposing to type 2 diabetes is ENPP1/PC1. A common polymorphism in this protein, K121Q, is associated with insulin resistance and increased susceptibility to type 2 diabetes in Caucasian, Afro-Caribbean, and South Asian populations. The goal of this study was to evaluate differences in the prevalence of the ENPP1 121Q variant in the Caucasian, African-American, and Hispanic populations in Dallas county and to establish a population-based estimate of gene variant prevalence for future investigations. We also evaluated the association between the ENPP1 121Q variant and diabetes. The Dallas Heart Study (DHS) is a multiethnic probability-based sample of the Dallas county population in which African-Americans were systematically oversampled so that the final sample was 50% African-Americans. We performed ENPP1/PC1 genotyping in 1038 non-Hispanic Whites (544 women, 494 men), 1815 African-Americans (1052 women and 763 men), and 597 Hispanics (347 women, 250 men). The frequency of ENPP1/PC1 K121Q was higher in both African-Americans (78.5%) and Hispanics (21.9%) than in the non-Hispanic White group (13.2%). The former two groups also have a higher prevalence of type 2 diabetes (African-Americans, 14.1%, and Hispanics, 11.7%) compared to non-Hispanic Whites (6.8%). Logistic regression analysis revealed significant interactions between the ENPP1 genotype, age, and body mass index within each ethnic group. After adjustment for these variables and their interactions, ENPP1 Q allele predicted diabetes when a recessive model was tested. Ethnic differences in ENPP1 121Q allele frequency may contribute to the increased susceptibility to type 2 diabetes observed in US minority groups.
authors.affiliation: Division of Endocrinology and Metabolism and The Center for Human Nutrition, Department of Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9169, USA. manisha.chandalia@utsouthwestern.edu
authors.forename: Manisha
authors.initials: M
authors.lastname: Chandalia
authors.forename: Scott M
authors.initials: SM
authors.lastname: Grundy
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.forename: Nicola
authors.initials: N
authors.lastname: Abate
mesh_terms: D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D014644:Genetic Variation; D006630:Hispanic or Latino; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D013781:Texas; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases