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ENPP1 K121Q Polymorphism is not Related to Type 2 Diabetes Mellitus, Features of Metabolic Syndrome, and Diabetic Cardiovascular Complications in a Chinese Population
 
Diabetes OD > Diabetic Complications > T2DM > Cardiovascular > Genetics > Ectoenzyme (ENPP1) > Journal Article

(Journal Article): ENPP1 K121Q Polymorphism is not Related to Type 2 Diabetes Mellitus, Features of Metabolic Syndrome, and Diabetic Cardiovascular Complications in a Chinese Population
 
Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ (Department of Clinical Research, Pingtung Christian Hospital, Pingtung, 90000 Taiwan, t3275@ms25.hinet.net )
 
IN: Rev Diabetic Stud 2006; 3(1):21-30
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)

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ABSTRACT: BACKGROUND: Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) is known to influence insulin sensitivity by inhibiting insulin receptor signaling. A DNA polymorphism in the ENPP1 gene at exon 4 (K121Q) was demonstrated to be associated with insulin resistance, type 2 diabetes mellitus (T2DM), and a risk of early myocardial infarction, albeit with controversy. Our aim was to investigate any association of ENPP1 K121Q alleles with T2DM, features of the metabolic syndrome, and diabetic cardiovascular complications in a Chinese population of Han origin. METHODS: The ENPP1 K121Q polymorphism was determined by a restriction fragment-length polymorphism-polymerase chain reaction in 1,862 patients with T2DM and 844 non-diabetic subjects. RESULTS: The genotype distributions or Q-allele frequency were not statistically different between the diabetic and non-diabetic groups. The anthropometric parameters, systolic and diastolic blood pressures, lipid profiles, and serum creatinine levels of subjects with different ENPP1 K121Q polymorphisms were not statistically different in the two groups or even in the pooled data. When sub-group analyses of diabetic subjects were stratified according to BMI levels (greater or less than 27), gender, age of diabetes onset (older or younger than 60 years), and the presence or absence of a diabetic family history; this polymorphism was still not associated with T2DM. Nor was the ENPP1 K121Q polymorphism associated with the prevalence of coronary artery disease and ischemic cerebrovascular disease in patients with T2DM. CONCLUSION: The ENPP1 K121Q polymorphism is not related to T2DM, features of the metabolic syndrome, or diabetic macrovascular complications in a Chinese population.

TYPE OF PUBLICATION: Original article

REFERENCES:

  1. Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA, et al. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 1995. 373:448-451.
  2. Dong H, Maddux BA, Altomonte J, Meseck M, Accili D, Terkeltaub R, Johnson K, Youngren JF, Goldfine ID. Increased hepatic levels of the insulin receptor inhibitor, PC-1/ENPP1, induce insulin resistance and glucose intolerance. Diabetes 2005. 54:367-372.
  3. Harahap AR, Goding JW. Distribution of the murine plasma cell antigen PC-1 in non-lymphoid tissues. J Immunol 1988. 141: 2317-2320.
  4. Maddux BA, Goldfine ID. Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit. Diabetes 2000. 49:13-19.
  5. Kumakura S, Maddux BA, Sung CK. Overexpression of membrane glycoprotein PC-1 can influence insulin action at a post-receptor site. J Cell Biochem 1998. 68:366-377.
  6. Frittitta L, Youngren JF, Sbraccia P, D’Adamo M, Buongiorno A, Vigneri R, Goldfine ID, Trischitta V. Increased adipose tissue PC-1 protein content, but not tumour necrosis factor-alpha gene expression, is associated with a reduction of both whole body insulin sensitivity and insulin receptor tyrosine-kinase activity. Diabetologia 1997. 40:282-289.
  7. Frittitta L, Spampinato D, Solini A, Nosadini R, Goldfine ID, Vigneri R, Trischitta V. Elevated PC-1 content in cultured skin fibroblasts correlates with decreased in vivo and in vitro insulin action in nondiabetic subjects: evidence that PC-1 may be an intrinsic factor in impaired insulin receptor signaling. Diabetes 1998. 47:1095-1110.
  8. Youngren J, Maddux BA, Sasson S, Sbraccia P, Tapscott EB, Swanson MS, Dohm LG, Goldfine ID. Skeletal muscle content of membrane glycoprotein PC-1 in obesity. Diabetes 1996. 45:1324-1328.
  9. Pizzuti A, Frittitta L, Argiolas A, Baratta R, Goldfine ID, Bozzali M, Ercolino T, Scarlato G, Iacoviello L, Vigneri R, et al. A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. Diabetes 1999. 48:1881-1884.
  10. Costanzo BV, Trischitta V, Di Paola R, Spampinato D, Pizzuti A, Vigneri R, Frittitta L. The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121). Diabetes 2001. 50:831-836.
  11. Abate N, Carulli L, Cabo-Chan A Jr, Chandalia M, Snell PG, Grundy SM. Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance. J Clin Endocrinol Metab 2003. 88:5927-5934.
  12. Gu HF, Almgren P, Lindholm E, Frittitta L, Pizzuti A, Trischitta V, Groop LC. Association between the human glycoprotein PC-1 gene and elevated glucose and insulin levels in a paired-sibling analysis. Diabetes 2000. 49:1601-1603.
  13. Kubaszek A, Pihlajamaki J, Karhapaa 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. 26:464-467.
  14. Meyre D, Bouatia-Naji N, Tounian A, Samson C, Lecoeur C, Vatin V, Ghoussaini M, Wachter C, Hercberg S, Charpentier G, 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. 37:863-867.
  15. Matsuoka N, Patki A, Tiwari HK, Allison DB, Johnson SB, Gregersen PK, Leibel RL, Chung WK. Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults. Int J Obes (Lond) 2005. 30(2):233-237.
  16. Endler G, Mannhalter C, Sunder-Plassmann H, Schillinger M, Klimesch A, Exner M, Kapiotis S, Meier S, Kunz F, Raiger E, et al. The K121Q polymorphism in the plasma cell membrane glycoprotein 1 gene predisposes to early myocardial infarction. J Mol Med 2002. 80:791-795.
  17. Bacci S, Ludovico O, Prudente S, Zhang YY, Di Paola R, Mangiacotti D, Rauseo A, Nolan D, Duffy J, Fini G, 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. 54:3021-3025.
  18. Rasmussen SK, Urhammer SA, Pizzuti A, Echwald SM, Ekstrom CT, Hansen L, Hansen T, Borch-Johnsen K, Frittitta L, Trischitta V, et al. The K121Q variant of the human PC-1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians. Diabetes 2000. 49:1608-1611.
  19. Gonzalez-Sanchez JL, Martinez-Larrad MT, 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. 11:603-605.
  20. Morrison JA, Gruppo R, Glueck CJ, Stroop D, Fontaine RN, Wang P, Smith KL. 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. 53:465-468.
  21. Kubaszek A, Markkanen A, Eriksson JG, Forsen T, Osmond C, Barker DJ, Laakso M. The association of the K121Q polymorphism of the plasma cell glycoprotein-1 gene with type 2 diabetes and hypertension depends on size at birth. J Clin Endocrinol Metab 2004. 89:2044-2047.
  22. Abate N, Chandalia M, Satija P, Adams-Huet B, Grundy SM, Sandeep S, Radha V, Deepa R, Mohan V. ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes. Diabetes 2005. 54:1207-1213.
  23. Hamaguchi K, Terao H, Kusuda Y, Yamashita T, Hazoury Bahles JA, Cruz LLM, Brugal VLI, Jongchong WB, Yoshimatsu H, Sakata T. The PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic and is associated with type 2 diabetes. J Clin Endocrinol Metab 2004. 89:1359-1364.
  24. Hegele RA, Harris SB, Zinman B, Hanley AJ, Cao H. Absence of association of type 2 diabetes with CAPN10 and PC-1 polymorphisms in Oji-Cree. Diabetes Care 2001. 24:1498-1499.
  25. Chung FM, Tsai JC, Chang DM, Shin SJ, Lee YJ. Peripheral total and differential leukocyte count in diabetic nephropathy: the relationship of plasma leptin to leukocytosis. Diabetes Care 2005. 28:1710-1717.
  26. Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ. Elevated Plasma Level of Visfatin/Pre-B Cell Colony-Enhancing Factor in Patients with Type 2 Diabetes Mellitus. J Clin Endocrinol Metab 2006. 91:295-299.
  27. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. 1. Diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation. Diabet Med 1998. 15:539-553.
  28. Laakso M, Pyorala K. Age of onset and type of diabetes. Diabetes Care 1985. 8:114-117.
  29. Chen MP, Tsai JC, Chung FM, Yang SS, Hsing LL, Shin SJ, Lee YJ. Hypoadiponectinemia is associated with ischemic cerebrovascular disease. Arterioscler Thromb Vasc Biol 2005. 25:821-826.
  30. Tsai JC, Chang DM, Chung FM, Wu JC, Shin SJ, Lee YJ. The Association of Silent Coronary Artery Disease and Metabolic Syndrome in Chinese with Type 2 Diabetes Mellitus. Rev Diabetic Stud 2004. 1:18-28.
  31. Hansen L, Pedersen O. Genetics of type 2 diabetes mellitus: status and perspectives. Diabetes Obes Metab 2005. 7:122-135.
  32. Hennis A, Wu SY, Nemesure B, Li X, Leske MC. Diabetes in a Caribbean population: epidemiological profile and implications. Int J Epidemiol 2002. 31:234-239.
  33. O'Rahilly S, Barroso I, Wareham NJ. Genetic factors in type 2 diabetes: the end of the beginning? Science 2005. 307:370-373.
  34. Wareham NJ, Franks PW, Harding AH. Establishing the role of gene-environment interactions in the etiology of type 2 diabetes. Endocrinol Metab Clin North Am 2002. 31:553-566.
  35. Stefanovic V, Antic S. Plasma cell membrane glycoprotein 1 (PC-1): a marker of insulin resistance in obesity, uremia and diabetes mellitus. Clin Lab 2004. 50:271-278.
  36. Kuller LH. Ethnic differences in atherosclerosis, cardiovascular disease and lipid metabolism. Curr Opin Lipidol 2004. 15:109-113.


 
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