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. 2008 Jul;16(7):1708-13.
doi: 10.1038/oby.2008.262. Epub 2008 May 8.

Association of genetic variation in ENPP1 with obesity-related phenotypes

Christopher P Jenkinson  1 , Dawn K Coletta, Marion Flechtner-Mors, Shirley L Hu, Marcel J Fourcaudot, Lenore M Rodriguez, Jennifer Schneider, Rector Arya, Michael P Stern, John Blangero, Ravindranath Duggirala, Ralph A DeFronzo
Affiliations

Association of genetic variation in ENPP1 with obesity-related phenotypes

Christopher P Jenkinson et al. Obesity (Silver Spring). 2008 Jul.

Abstract

Ectonucleotide pyrophosphatase phosphodiesterase (ENPP1) is a positional candidate gene at chromosome 6q23 where we previously detected strong linkage with fasting-specific plasma insulin and obesity in Mexican Americans from the San Antonio Family Diabetes Study (SAFDS). We genotyped 106 single-nucleotide polymorphisms (SNPs) within ENPP1 in all 439 subjects from the linkage study, and measured association with obesity and metabolic syndrome (MS)-related traits. Of 72 polymorphic SNPs, 24 were associated, using an additive model, with at least one of eight key metabolic traits. Three traits were associated with at least four SNPs. They were high-density lipoprotein cholesterol (HDL-C), leptin, and fasting plasma glucose (FPG). HDL-C was associated with seven SNPs, of which the two most significant P values were 0.0068 and 0.0096. All SNPs and SNP combinations were analyzed for functional contribution to the traits using the Bayesian quantitative-trait nucleotide (BQTN) approach. With this SNP-prioritization analysis, HDL-C was the most strongly associated trait in a four-SNP model (P=0.00008). After accounting for multiple testing, we conclude that ENPP1 is not a major contributor to our previous linkage peak with MS-related traits in Mexican Americans. However, these results indicate that ENPP1 is a genetic determinant of these traits in this population, and are consistent with multiple positive association findings in independent studies in diverse human populations.

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Conflict of interest statement

Disclosure: The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
SNP linkage disequilibrium structure within ENPP1. SNPs are indicated by their physical order within the gene on the y-axis. The relative positions of the SNPs are indicated on the x-axis. Physical distance is denoted in bp. The degree of correlation (ρ) between SNP pairs is indicated by the intensity of shading in the small squares of the central figure, with perfect correlation between identical SNPs along the diagonal. Gene exonic structure is indicated by the vertical bars below the x-axis. A total of 79 SNPs are shown, including seven SNPs which were not in Hardy–Weinberg equilibrium.
Figure 2
Figure 2
Gene structure of ENPP1 and location of significantly associated SNPs. SNPs exhibiting significant nominal association (P < 0.05) are shown. The thick horizontal line represents the gene, with thick vertical lines representing the 25 exons, numbered below each exon.
Figure 3
Figure 3
Association of ENPP1 SNPs with (a) HDL-C and (b) FPG. The physical location of each SNP is shown on the x-axis. The y-axis shows –log10 P values for association calculated using the measured genotype approach.
See this image and copyright information in PMC

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