Effect of the rs997509 Polymorphism on the Association between Ectonucleotide Pyrophosphatase Phosphodiesterase 1 and Metabolic Syndrome and Impaired Glucose Tolerance in Childhood Obesity

Santoro, Nicola; Cirillo, Grazia; Lepore, María Grazia; Palma, A. De; Amato, Alessandra; Savarese, Piera; Marzuillo, Pierluigi; Grandone, Anna; Perrone, Laura; Giudice, Emanuele Miraglia del

doi:10.1210/jc.2008-1659

Cited by 22 publications

(15 citation statements)

References 30 publications

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“…Triglyceride, high-density lipoprotein (HDL) cholesterol, insulin, and glycemia levels were measured as previously described (27,28). Insulin resistance was assessed using the homeostasis model assessment (HOMA-IR), with a cut-off value of 3 (29).…”

Section: Patientsmentioning

confidence: 99%

Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation

Rossi¹,

Bellini

Luongo

et al. 2016

The Journal of Clinical Endocrinology &Amp; Metabolism

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Section: Patientsmentioning

confidence: 99%

Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation

Rossi¹,

Bellini

Luongo

et al. 2016

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…[6][7][8][9] ENPP1 lies on chromosome 6q22-q23 (OMIM#173335) in a region where several independent studies found a linkage peak to OB phenotypes. [10][11][12][13] ENPP1 is an attractive candidate gene for studying OB, as it was proposed as a key player in the etiology of insulin resistance 14,15 and in a recently suggested mechanism underlying defective adipocyte maturation.…”

Section: Introductionmentioning

confidence: 99%

Morphological and biochemical features of obesity are associated with mineralization genes’ polymorphisms

et al. 2010

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Background: Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was recently extensively studied as a candidate gene for obesity phenotypes. As the human homologue of the mouse progressive ankylosis (ANKH) and alkaline phosphatase (ALPL) are known functional partners of ENPP1 in bone mineralization, we hypothesized that these genes may also be jointly involved in determining obesity features. Aim: To examine the effects of the three genes, possible gene-sex and gene-gene interactions on variability of four obesity phenotypes: the body mass index (BMI), the waist-hip ratio (WHR), the epidermal growth factor receptor (EGFR), and leptin. Subjects and methods: In all, 962 healthy individuals from 230 families were genotyped for 45 single nucleotide polymorphisms (SNPs). The association analysis was performed using two family based association tests (family based association test and pedigree disequilibrium test). The combined P-values of the two tests were estimated by Monte-Carlo simulations. Relative magnitude of the genetic and familial effects, gene-sex and gene-gene interactions were assessed using variance component models. Results: Associations were observed between ENPP1 polymorphisms and BMI (P ¼ 0.0037) and leptin (P ¼ 0.0068). ALPL markers were associated with WHR (P ¼ 0.0026) and EGFR (P ¼ 0.0001). The ANKH gene was associated with all four studied obesity-related traits (Po0.0184), and its effects were modulated by sex. Gene-gene interactions were not detected. Conclusion: The observed pattern of association signals indicates that ANKH may have a generalized effect on adipose tissue physiology, whereas ENPP1 and ALPL affect distinct obesity features. The joint analysis of related genes and integration of the results obtained by different methods used in this research should benefit other studies of similar design.

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“…Santoro and cols. (63), studying lean and obese children, ob served that those who were carriers of the rs997509 T allele of ENPP1 gene presented higher levels of plasma insulin and HOMAIR (homeostasis model assessment -insulin resistance) and lower insulin sensitivity index compared with children who were homozygous for the most common allele. A similar observation was made for the Q variant of K121 polymorphism.…”

Section: Other Polymorphisms In Enpp1 Gene Associated With Diabetes Mmentioning

confidence: 99%

“…Besides, chil dren carrying the rare rs997509 T allele were at higher risk of developing metabolic syndrome and impaired glucose tolerance than children who were homozygous for the common allele. Evaluating the combined effects of polymorphisms rs997509 and K121Q, which are in strong disequilibrium linkage, the authors demonstra ted that the effect on insulin sensitivity was due to the presence of the rs997509 T allele and not due to the K121Q polymorphism (63).…”

Section: Other Polymorphisms In Enpp1 Gene Associated With Diabetes Mmentioning

confidence: 99%

The role of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 in diabetic nephropathy

Sortica

Crispim

Zaffari

et al. 2011

Arq Bras Endocrinol Metab

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SUMMARYThe increased prevalence of diabetes mellitus has caused a rise in the occurrence of its chronic complications, such as diabetic nephropathy (DN), which is associated with elevated morbidity and mortality. Familial aggregation studies have demonstrated that besides the known environmental risk factors, DN has a major genetic component. Therefore, it is necessary to identify genes associated with risk for or protection against DN. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is expressed in several tissues, including the kidneys. Increased levels of ENPP1 expression inhibit tyrosine-kinase activity of the insulin receptor in several cell types, leading to insulin resistance. K121Q polymorphism of the ENPP1 gene seems to be associated with insulin resistance and DN development. The elucidation of genetic factors and their associations will provide better understanding of the pathogenesis of DN and, may consequently, lead to a more effective approach to prevention and treatment. Arq Bras Endocrinol Metab. 2011;55(9):677-85 Keywords ENPP1; diabetic nephropathy; diabetes mellitus; DNA polymorphisms; chronic renal disease; insulin resistance SUMÁRIO A crescente prevalência do diabetes melito tem causado aumento na ocorrência das suas complicações crônicas, como a nefropatia diabética (ND), a qual está associada com elevada morbidade e mortalidade. Estudos de agregação familiar demonstram que a ND tem um importante componente genético, além dos conhecidos fatores de risco ambientais. Portanto, existe a necessidade de se identificarem genes associados ao risco ou proteção à ND. A ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) é expressa em vários tecidos, incluindo nos rins. Foi encontrado que níveis aumentados de expressão da ENPP1 inibem a atividade tirosino-quinase do receptor da insulina em vários tipos celulares, causando resistência à insulina. O polimorfismo K121Q do gene ENNP1 parece estar associado com resistência à insulina e com o desenvolvimento da ND. A elucidação dos fatores genéticos e de suas associações permitirá um melhor entendimento da patogênese da ND e, consequentemente, poderemos ter uma abordagem mais efetiva em sua prevenção e tratamento. Arq Bras Endocrinol Metab. 2011;55(9):677-85

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Effect of the rs997509 Polymorphism on the Association between Ectonucleotide Pyrophosphatase Phosphodiesterase 1 and Metabolic Syndrome and Impaired Glucose Tolerance in Childhood Obesity

Abstract: We conclude that the ENPP1 rs997509T allele can predispose obese children to MS and IGT and that this variant might drive the association between the ENPP1 121Q allele and insulin resistance.

Cited by 22 publications

References 30 publications

Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation

Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation

Morphological and biochemical features of obesity are associated with mineralization genes’ polymorphisms

The role of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 in diabetic nephropathy

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