Association of genetic variation in ENPP1 with obesity-related phenotypes

Christopher P. Jenkinson, 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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1708-1713
Number of pages6
JournalObesity
Volume16
Issue number7
DOIs
StatePublished - Jul 2008

Fingerprint

Single Nucleotide Polymorphism
Obesity
Phenotype
HDL Cholesterol
Fasting
Pyrophosphatases
Phosphoric Diester Hydrolases
Leptin
Population
Nucleotides
Chromosomes
Insulin
Glucose
Genes

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Jenkinson, C. P., Coletta, D. K., Flechtner-Mors, M., Hu, S. L., Fourcaudot, M. J., Rodriguez, L. M., ... Defronzo, R. A. (2008). Association of genetic variation in ENPP1 with obesity-related phenotypes. Obesity, 16(7), 1708-1713. https://doi.org/10.1038/oby.2008.262

Association of genetic variation in ENPP1 with obesity-related phenotypes. / Jenkinson, Christopher P.; Coletta, Dawn K.; Flechtner-Mors, Marion; Hu, Shirley L.; Fourcaudot, Marcel J.; Rodriguez, Lenore M.; Schneider, Jennifer; Arya, Rector; Stern, Michael P.; Blangero, John; Duggirala, Ravindranath; Defronzo, Ralph A.

In: Obesity, Vol. 16, No. 7, 07.2008, p. 1708-1713.

Research output: Contribution to journalArticle

Jenkinson, CP, Coletta, DK, Flechtner-Mors, M, Hu, SL, Fourcaudot, MJ, Rodriguez, LM, Schneider, J, Arya, R, Stern, MP, Blangero, J, Duggirala, R & Defronzo, RA 2008, 'Association of genetic variation in ENPP1 with obesity-related phenotypes', Obesity, vol. 16, no. 7, pp. 1708-1713. https://doi.org/10.1038/oby.2008.262
Jenkinson CP, Coletta DK, Flechtner-Mors M, Hu SL, Fourcaudot MJ, Rodriguez LM et al. Association of genetic variation in ENPP1 with obesity-related phenotypes. Obesity. 2008 Jul;16(7):1708-1713. https://doi.org/10.1038/oby.2008.262
Jenkinson, Christopher P. ; Coletta, Dawn K. ; Flechtner-Mors, Marion ; Hu, Shirley L. ; Fourcaudot, Marcel J. ; Rodriguez, Lenore M. ; Schneider, Jennifer ; Arya, Rector ; Stern, Michael P. ; Blangero, John ; Duggirala, Ravindranath ; Defronzo, Ralph A. / Association of genetic variation in ENPP1 with obesity-related phenotypes. In: Obesity. 2008 ; Vol. 16, No. 7. pp. 1708-1713.
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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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