Genomes and Genes
Gene Symbol: PC 1
Description: ectonucleotide pyrophosphatase/phosphodiesterase 1
Alias: ARHR2, COLED, M6S1, NPP1, NPPS, PC-1, PCA1, PDNP1, ectonucleotide pyrophosphatase/phosphodiesterase family member 1, E-NPP 1, Ly-41 antigen, alkaline phosphodiesterase 1, membrane component, chromosome 6, surface marker 1, phosphodiesterase I/nucleotide pyrophosphatase 1, plasma-cell membrane glycoprotein 1, plasma-cell membrane glycoprotein PC-1
Products: PC 1
- Grarup N, Urhammer S, Ek J, Albrechtsen A, Glumer C, Borch Johnsen K, et al. Studies of the relationship between the ENPP1 K121Q polymorphism and type 2 diabetes, insulin resistance and obesity in 7,333 Danish white subjects. Diabetologia. 2006;49:2097-104 pubmedb>Plasma cell membrane glycoprotein 1 (PC-1) inhibits insulin signalling by direct interaction with the insulin receptor alpha subunit...
- Abate N, Carulli L, Cabo Chan A, Chandalia M, Snell P, Grundy S. Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance. J Clin Endocrinol Metab. 2003;88:5927-34 pubmed..This finding indicates the need for expanded studies on the association between PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian population. ..
- Maddux B, Goldfine I. Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit. Diabetes. 2000;49:13-9 pubmed..These studies also raise the possibility that monoclonal antibodies to PC-1 could be a new treatment for insulin resistance. ..
- Maddux B, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, et al. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature. 1995;373:448-51 pubmed..These studies raise the possibility that PC-1 has a role in the insulin resistance of non-insulin-dependent diabetes mellitus. ..
- Huang R, Rosenbach M, Vaughn R, Provvedini D, Rebbe N, Hickman S, et al. Expression of the murine plasma cell nucleotide pyrophosphohydrolase PC-1 is shared by human liver, bone, and cartilage cells. Regulation of PC-1 expression in osteosarcoma cells by transforming growth factor-beta. J Clin Invest. 1994;94:560-7 pubmed..The identification of PC-1 as an NTPPPH expressed in cells derived from bone and cartilage may prove useful in furthering the understanding of the role of NTPPPH i n physiologic and pathologic mineralization. ..
- Morrison J, Gruppo R, Glueck C, Stroop D, Fontaine R, Wang P, et al. Population-specific alleles: the polymorphism (K121Q) of the human glycoprotein PC-1 gene is strongly associated with race but not with insulin resistance in black and white children. Metabolism. 2004;53:465-8 pubmed..However, the QQ genotype was population-specific, encompassing most black children versus 1% to 3% of white children. As such, K121Q genotyping should be useful in epidemiology, population genetics, and forensic anthropology. ..
- Buckley M, Loveland K, McKinstry W, Garson O, Goding J. Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location. J Biol Chem. 1990;265:17506-11 pubmed..Southern blots suggest a single copy gene. In situ chromosomal hybridization localizes the gene for human PC-1 to chromosome 6q22-q23, a common site for deletions in human lymphoid neoplasia. ..
- Liang J, Fu M, Ciociola E, Chandalia M, Abate N. Role of ENPP1 on adipocyte maturation. PLoS ONE. 2007;2:e882 pubmed..We identify ENPP1 as a novel mechanism of defective adipocyte maturation. This mechanism could contribute to the pathogenesis of insulin resistance in absence of obesity. ..
- Abate N, Chandalia M, Di Paola R, Foster D, Grundy S, Trischitta V. Mechanisms of disease: Ectonucleotide pyrophosphatase phosphodiesterase 1 as a 'gatekeeper' of insulin receptors. Nat Clin Pract Endocrinol Metab. 2006;2:694-701 pubmed..The transmembrane glycoprotein ectonucleotide pyrophosphatase phosphodiesterase 1 (E-NPP1; also known as plasma cell membrane glycoprotein PC-1) interacts with the insulin receptor and inhibits subsequent ..
- Lin C, Wu C, Wu L. Ectonucleotide pyrophosphatase/phosphodiesterase 1 K173Q polymorphism is associated with diabetic nephropathy in the Taiwanese population. Genet Test Mol Biomarkers. 2011;15:239-42 pubmed publisher..We confirmed the association between the rs1044498 SNP in ENPP1 and diabetic nephropathy, especially among obese diabetic patients, in the Taiwanese population. ..
- Chen M, Chung F, Chang D, Tsai J, Huang H, Shin S, et al. ENPP1 K121Q polymorphism is not related to type 2 diabetes mellitus, features of metabolic syndrome, and diabetic cardiovascular complications in a Chinese population. Rev Diabet Stud. 2006;3:21-30 pubmed..The ENPP1 K121Q polymorphism is not related to T2DM, features of the metabolic syndrome, or diabetic macrovascular complications in a Chinese population. ..
- Chin C, Dallas Yang Q, Liu F, Ho T, Ellsworth K, Fischer P, et al. Evidence that inhibition of insulin receptor signaling activity by PC-1/ENPP1 is dependent on its enzyme activity. Eur J Pharmacol. 2009;606:17-24 pubmed publisher..Together, these results suggest that the inhibition of insulin signaling by PC-1 is somewhat specific and is dependent upon the enzymatic activity of the phosphodiesterase/pyrophosphatase. ..
- Stolerman E, Manning A, McAteer J, Dupuis J, Fox C, Cupples L, et al. Haplotype structure of the ENPP1 Gene and Nominal Association of the K121Q missense single nucleotide polymorphism with glycemic traits in the Framingham Heart Study. Diabetes. 2008;57:1971-7 pubmed publisher..We found an adiposity-SNP interaction, with a stronger association of K121Q with diabetes-related quantitative traits in people with a higher BMI. ..
- McAteer J, Prudente S, Bacci S, Lyon H, Hirschhorn J, Trischitta V, et al. The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European populations: evidence from an updated meta-analysis in 42,042 subjects. Diabetes. 2008;57:1125-30 pubmed..93 [95% CI 0.75-1.15], P = 0.50). The ENPP1 Q121 variant increases risk of type 2 diabetes under a recessive model of inheritance in whites, an effect that appears to be modulated by BMI. ..
- Rutsch F, Vaingankar S, Johnson K, Goldfine I, Maddux B, Schauerte P, et al. PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification. Am J Pathol. 2001;158:543-54 pubmed
- Bacci S, De Cosmo S, Prudente S, Trischitta V. ENPP1 gene, insulin resistance and related clinical outcomes. Curr Opin Clin Nutr Metab Care. 2007;10:403-9 pubmed
- Weedon M, Shields B, Hitman G, Walker M, McCarthy M, Hattersley A, et al. No evidence of association of ENPP1 variants with type 2 diabetes or obesity in a study of 8,089 U.K. Caucasians. Diabetes. 2006;55:3175-9 pubmed..25 [1.10-1.43], P = 0.0007), although there was some evidence of publication bias. In conclusion, we find no evidence that previously associated variants of ENPP1 are associated with type 2 diabetes or obesity in the U.K. population. ..
- Meyre D, Bouatia Naji N, Tounian A, Samson C, Lecoeur C, Vatin V, et al. Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nat Genet. 2005;37:863-7 pubmed..These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions. ..
- Keshavarz P, Inoue H, Sakamoto Y, Kunika K, Tanahashi T, Nakamura N, et al. No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population. J Hum Genet. 2006;51:559-66 pubmed..3). Our results indicated that the K121Q variant of the ENPP1 gene has very little, if any, impact on T2D susceptibility in Japanese, but may play a role in the inter-ethnic variability in insulin resistance and T2D. ..
- Levy Litan V, Hershkovitz E, Avizov L, Leventhal N, Bercovich D, Chalifa Caspi V, et al. Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene. Am J Hum Genet. 2010;86:273-8 pubmed publisher..Our surprising result suggests a different pathway involved in the generation of ARHR and possible additional functions for ENPP1. ..
- Endler G, Mannhalter C, Sunder Plassmann H, Schillinger M, Klimesch A, Exner M, et al. The K121Q polymorphism in the plasma cell membrane glycoprotein 1 gene predisposes to early myocardial infarction. J Mol Med (Berl). 2002;80:791-5 pubmedElevated plasma cell membrane glycoprotein 1 (PC-1) expression and the frequent PC-1 K121Q polymorphism have recently been associated with insulin resistance...
- Sortica D, Crispim D, Zaffari G, Friedman R, Canani L. The role of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 in diabetic nephropathy. Arq Bras Endocrinol Metabol. 2011;55:677-85 pubmed..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. ..
- Bacci S, Rizza S, Prudente S, Spoto B, Powers C, Facciorusso A, et al. The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: evidence for interaction with obesity in diabetic patients. Diabetes. 2011;60:1000-7 pubmed publisher..The ENPP1 K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding. ..
- De Cosmo S, Minenna A, Zhang Y, Thompson R, Thompson R, Miscio G, et al. Association of the Q121 variant of ENPP1 gene with decreased kidney function among patients with type 2 diabetes. Am J Kidney Dis. 2009;53:273-80 pubmed publisher..04). P values not approaching a genome-wide level of significance. Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR. ..
- Kubaszek A, Pihlajamaki J, Karhapää P, Vauhkonen I, Laakso M. The K121Q polymorphism of the PC-1 gene is associated with insulin resistance but not with dyslipidemia. Diabetes Care. 2003;26:464-7 pubmed..In healthy normoglycemic Finnish subjects, the K121Q polymorphism of the PC-1 gene is associated with insulin resistance but not with impaired insulin secretion or dyslipidemia. ..
- Rutsch F, Ruf N, Vaingankar S, Toliat M, Suk A, Hohne W, et al. Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification. Nat Genet. 2003;34:379-81 pubmed..This cell surface enzyme generates inorganic pyrophosphate (PP(i)), a solute that regulates cell differentiation and serves as an essential physiologic inhibitor of calcification. ..
- Bottcher Y, Körner A, Reinehr T, Enigk B, Kiess W, Stumvoll M, et al. ENPP1 variants and haplotypes predispose to early onset obesity and impaired glucose and insulin metabolism in German obese children. J Clin Endocrinol Metab. 2006;91:4948-52 pubmed..In conclusion, our study suggests a potential role of the K121Q polymorphism or derived ENPP1 haplotypes in increased susceptibility to obesity and early impairment of glucose and insulin metabolism in children. ..
- Lorenz Depiereux B, Schnabel D, Tiosano D, Häusler G, Strom T. Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet. 2010;86:267-72 pubmed publisher..Surprisingly, ENPP1 loss-of-function mutations have previously been described in generalized arterial calcification of infancy, suggesting an as yet elusive mechanism that balances arterial calcification with bone mineralization. ..
- Abate N, Chandalia M, Satija P, Adams Huet B, Grundy S, Sandeep S, et al. ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes. Diabetes. 2005;54:1207-13 pubmed
- Wu L, Hsieh C, Pei D, Hung Y, Kuo S, Lin E. Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARgamma and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes. Nephrol Dial Transplant. 2009;24:3360-6 pubmed publisher..The results suggest that the SNPs from the T2D-related genes may contribute to the risk of DN in T2D independently and/or in an interactive manner in Taiwanese T2D patients. ..
- Marucci A, Miscio G, Padovano L, Boonyasrisawat W, Florez J, Doria A, et al. The role of HSP70 on ENPP1 expression and insulin-receptor activation. J Mol Med (Berl). 2009;87:139-144 pubmed publisher..Taken together these data suggest that HSP70, by affecting ENPP1 expression, may be a novel mediator of altered insulin signaling. ..
- Gonzalez Sanchez J, Martinez Larrad M, Fernandez Perez C, Kubaszek A, Laakso M, Serrano Rios M. K121Q PC-1 gene polymorphism is not associated with insulin resistance in a Spanish population. Obes Res. 2003;11:603-5 pubmed..The results showed that the K121Q PC-1 polymorphism in the Spanish population has no significant impact on insulin sensitivity. ..
- Bouhaha R, Meyre D, Kamoun H, Ennafaa H, Vaillant E, Sassi R, et al. Effect of ENPP1/PC-1-K121Q and PPARgamma-Pro12Ala polymorphisms on the genetic susceptibility to T2D in the Tunisian population. Diabetes Res Clin Pract. 2008;81:278-83 pubmed publisher..25-0.97], p=0.02). In conclusion, our findings support the hypothesis that ENPP1-121Q is involved in the genetic susceptibility of T2D in the Tunisian population, while the PPARgamma-12Ala allele may confer protection against overweight. ..
- Dong H, Maddux B, Altomonte J, Meseck M, Accili D, Terkeltaub R, et al. Increased hepatic levels of the insulin receptor inhibitor, PC-1/NPP1, induce insulin resistance and glucose intolerance. Diabetes. 2005;54:367-72 pubmed..These in vivo data support the concept, therefore, that PC-1 plays a role in insulin resistance and suggest that animals with overexpression of human PC-1 in liver may be interesting models to investigate this pathological process. ..
- Bacci S, Ludovico O, Prudente S, Zhang Y, Di Paola R, Mangiacotti D, et al. The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction. Diabetes. 2005;54:3021-5 pubmed..In conclusion, the ENPP1/PC-1 121Q variant is associated with a progressive deterioration of the IR-atherogenic phenotype; among diabetic individuals, it is also associated with earlier onset of type 2 diabetes and MI. ..
- Meyre D, Bouatia Naji N, Vatin V, Veslot J, Samson C, Tichet J, et al. ENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study. Diabetologia. 2007;50:2090-6 pubmed
- Jacobsen P, Grarup N, Tarnow L, Parving H, Pedersen O. PC-1 amino acid variant (K121Q) has no impact on progression of diabetic nephropathy in type 1 diabetic patients. Nephrol Dial Transplant. 2002;17:1408-12 pubmed..27], whereas the PC-1 genotype did not contribute. Our study did not reveal an association between the PC-1 amino acid variant K121Q and progression of diabetic nephropathy. ..
- Bochenski J, Placha G, Wanic K, Malecki M, Sieradzki J, Warram J, et al. New polymorphism of ENPP1 (PC-1) is associated with increased risk of type 2 diabetes among obese individuals. Diabetes. 2006;55:2626-30 pubmed..In conclusion, we found a new SNP, rs997509, in intron 1 that is strongly associated with risk of type 2 diabetes in obese individuals. The molecular mechanisms underlying this association are unknown. ..
- Moehlecke M, Kramer C, Leitao C, Krahe A, Balbosco I, Azevedo M, et al. [ENPP1 K121Q polymorphism and ischemic heart disease in diabetic patients]. Arq Bras Cardiol. 2010;94:157-61, 168-73, 159-63 pubmed..No association was found between polymorphism K121A of ENPP1 gene and the presence of IHD. ..
- Wang M, Peng C, Qu Y, Huang Q. [Association and meta-analysis of ENPP1 K121Q with type 2 diabetes in Han Chinese.]. Yi Chuan. 2010;32:808-16 pubmed..The first meta-analysis of 10 Chinese studies indicated that the Q allele increased the risk of type 2 diabetes (OR=1.42, P=0.042). ..
- Zhao T, Liu Z, Zhang D, Liu Y, Yang Y, Zhou D, et al. The ENPP1 K121Q polymorphism is not associated with type 2 diabetes or obesity in the Chinese Han population. J Hum Genet. 2011;56:12-6 pubmed publisher..The ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene, also known as plasma cell membrane glycoprotein 1, has been reported by genetic association studies as being associated with T2D and obesity in ..
- Lee J, Choi Y, Seo H, Jeon J, Jeong J, Moon S, et al. Impact of ENPP1 and MMP3 gene polymorphisms on aortic calcification in patients with type 2 diabetes in a Korean population. Diabetes Res Clin Pract. 2010;88:87-96 pubmed publisher..001). Our study demonstrates that the ENPP1 K121Q and MMP3 -709A>G polymorphisms are associated with T2D, and that the ENPP1 Q allele is associated with increased aortic arch calcification in a Korean population. ..
- Maranghi M, Prudente S, D Erasmo L, Morini E, Ciociola E, Coletta P, et al. The ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism modulates the beneficial effect of weight loss on fasting glucose in non-diabetic individuals. Nutr Metab Cardiovasc Dis. 2013;23:505-10 pubmed publisher..This reinforces the previously suggested hypothesis that the Q121 variant interacts with adiposity in modulating glucose homeostasis. ..
- Moore A, Jablonski K, Mason C, McAteer J, Arakaki R, Goldstein B, et al. The association of ENPP1 K121Q with diabetes incidence is abolished by lifestyle modification in the diabetes prevention program. J Clin Endocrinol Metab. 2009;94:449-55 pubmed publisher..08; and HR, 1.16 (95% CI, 0.92-1.45), P = 0.20, respectively] but did not reach statistical significance. ENPP1 K121Q is associated with increased diabetes incidence; the DPP lifestyle intervention eliminates this increased risk. ..
- Baratta R, Rossetti P, Prudente S, Barbetti F, Sudano D, Nigro A, et al. Role of the ENPP1 K121Q polymorphism in glucose homeostasis. Diabetes. 2008;57:3360-4 pubmed publisher..Reduced early-phase insulin secretion and inefficient interplay between insulin secretion and sensitivity, which occur at early ages, are major determinants of this defect. ..
- Chandalia M, Grundy S, Adams Huet B, Abate N. Ethnic differences in the frequency of ENPP1/PC1 121Q genetic variant in the Dallas Heart Study cohort. J Diabetes Complications. 2007;21:143-8 pubmed..Ethnic differences in ENPP1 121Q allele frequency may contribute to the increased susceptibility to type 2 diabetes observed in US minority groups. ..
- Prudente S, Chandalia M, Morini E, Baratta R, Dallapiccola B, Abate N, et al. The Q121/Q121 genotype of ENPP1/PC-1 is associated with lower BMI in non-diabetic whites. Obesity (Silver Spring). 2007;15:1-4 pubmed..008). These data suggest that the QQ genotype of the ENPP1/PC-1 gene is associated with lower BMI. If similar results are confirmed in prospective studies, the K121Q polymorphism may help identify people at risk for obesity. ..
- Matsuoka N, Patki A, Tiwari H, Allison D, Johnson S, Gregersen P, et al. Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults. Int J Obes (Lond). 2006;30:233-7 pubmed..37) in obese subjects. In both Caucasians and African-Americans, the K121 polymorphism in ENPP1 was associated with increased BMI, but not with diabetes. ..
- Hamaguchi K, Terao H, Kusuda Y, Yamashita T, Hazoury Bahles J, Cruz LL M, et al. The PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic and is associated with type 2 diabetes. J Clin Endocrinol Metab. 2004;89:1359-64 pubmed..043; odds ratio = 2.74), but not obesity (P = 0.068). These results indicate that the PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic, contributing to both insulin resistance and type 2 diabetes. ..
- Lyon H, Florez J, Bersaglieri T, Saxena R, Winckler W, Almgren P, et al. Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity. Diabetes. 2006;55:3180-4 pubmed..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. ..
- Li Y. ENPP1 K121Q polymorphism and type 2 diabetes mellitus in the Chinese population: a meta-analysis including 11,855 subjects. Metabolism. 2012;61:625-33 pubmed publisher..0005). In the Chinese population, the ENPP1 K121Q gene polymorphism was implied to be involved with T2D susceptibility. People with the Q allele of the ENPP1 K121Q gene might be predisposed to T2D. ..
- Pizzuti A, Frittitta L, Argiolas A, Baratta R, Goldfine I, Bozzali M, et al. A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. Diabetes. 1999;48:1881-4 pubmed