Horm Metab Res 2006; 38(8): 524-529
DOI: 10.1055/s-2006-949524
Original Clinical

© Georg Thieme Verlag KG Stuttgart · New York

The K121Q Polymorphism of the Plasma Cell Glycoprotein-1 Gene is not Associated with Diabetes Mellitus Type 2 in German Caucasians

I. Gouni-Berthold 1 , E. Giannakidou 1 , M. Faust 1 , H. K. Berthold 2 , W. Krone 1
  • 1Department of Internal Medicine II, University of Cologne and Center of Molecular Medicine Cologne (CMMC), Germany
  • 2Drug Commission of the German Medical Association, Berlin, Germany
Further Information

Publication History

Received 5 September 2005

Accepted after revision 3 January 2006

Publication Date:
29 August 2006 (online)

Abstract

The K121Q polymorphism of the human plasma cell membrane glycoprotein 1 (PC-1) gene is known to be associated with diabetes mellitus type 2 in some populations studied, with contradictory results. The purpose of the present study was to examine a possible association between the presence of diabetes and the PC-1 K121Q polymorphism in a German Caucasian population. Associations between the polymorphism and various metabolic and anthropometric parameters were also examined. The presence of the K121Q variant was investigated using polymerase chain reaction restriction fragment-length polymorphism in 402 subjects with diabetes (231 men, 171 women, age 63±11 yrs, body mass index 28.7±5.1 kg/m2) and in 432 age- and sex-matched controls (247 men, 185 women, age 64±7 yrs, BMI 26.5±3.7 kg/m2). Ninety-seven subjects were carriers of the K121Q polymorphism in the control and 110 in the diabetic group (allelic frequency 11.9% and 14.7%, respectively, P=0.25). The polymorphism had no significant influence on the presence of atherosclerotic disease, body mass index, and blood pressure, both, in diabetics and in non-diabetic controls. Our data suggest that the K121Q polymorphism of the PC-1 gene is not associated with diabetes, obesity, hypertension or atherosclerosis in a German Caucasian population.

References

  • 1 Reaven G. Role of insulin resistance in human disease.  Diabetes. 1988;  37 1595-1607
  • 2 Beck-Nielsen H, Groop LC. Metabolic and genetic characterization of prediabetic states. Sequence of events leading to non-insulin-dependent diabetes mellitus.  J Clin Invest. 2004;  1994 1714-1721
  • 3 Almind K, Doria A, Khan CR. Putting the genes for type II diabetes on the map.  Nat Med. 2001;  7 277-279
  • 4 Frittitta L, Youngren J, Vigneri R, Maddux BA, Trischitta V, Goldfine ID. PC-1 content in skeletal muscle of non-obese, non-insulin-dependent diabetes mellitus.  Diabetologia. 1996;  39 1190-1195
  • 5 Frittitta L, Youngren J, Sbraccia P, D'Adamo M, Buongiorno A, Vigner R, Goldfine ID, Trischitta V. Increased adipose tissue PC-1 protein content, but not tumor necrosis factor-a gene expression, is associated with a reduction of both insulin sensitivity and insulin receptor tyrosine kinase activity.  Diabetologia. 1997;  40 282-289
  • 6 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 1095-1100
  • 7 Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA, Reaven G, Goldfine IG. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus.  Nature. 1995;  373 448-451
  • 8 Shao J, Catalano PM, Yamashita H, Ruyter I, Smith S, Youngren J, Friedman JE. Decreased insulin receptor tyrosine kinase activity and plasma cell membrane glycoprotein-1 overexpression in skeletal muscle from obese women and gestational diabetes mellitus (GDM): evidence for increased serine/threonine phosphorylation in pregnancy and GDM.  Diabetes. 2000;  49 603-610
  • 9 Teno S, Kanno H, Oga S, Kumakura S, Kanamuro R, Iwamoto Y. Increased activity of membrane glycoprotein PC-1 in the fibroblasts from non-insulin dependent diabetes mellitus patients with insulin resistance.  Diabetes Res Clin Pract. 1999;  45 25-30
  • 10 Youngren J, Maddux BA, Sasson S, Sbraccia P, Tapscott EB, Swanson MS, Dohm GL, Goldfine ID. Skeletal muscle content of membrane glycoprotein PC-1 in obesity.  Diabetes. 1996;  45 1324-1328
  • 11 Maddux B, Goldfine ID. Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor α-subunit.  Diabetes. 2000;  49 13-19
  • 12 Ottensmeyer FP, Beniac DR, Luo RZT, Yip CC. Mechanism of transmembrane signaling: insulin binding and the insulin receptor.  Biochemistry. 2000;  39 12103-12112
  • 13 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
  • 14 Frittitta L, Camastra S, Baratta R, Costanzo BV, D'Adamo M, Graci S, Spampinato D, Maddux BA, Vigneri R, Ferraninin E, Trischitta V. A soluble PC-1 circulates in human plasma: relationship with insulin resistance and associated abnormalities.  J Clin Endocrinol Metab. 1999;  84 3620-3625
  • 15 Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA, Reaven G, Goldfine IG. Membrane glycoprotein PC-1and insulin resistance in non-insulin-dependent diabetes mellitus.  Nature. 1995;  373 448-451
  • 16 Sakoda H, Oghara T, Anai M, Funaki M, Inukai K, Katagiri H, Fukushima Y, Onishi Y, Ono H, Yazaki Y, Kikuchi M, Oka Y, Asano T. No correlation of plasma cell 1 overexpression with insulin resistance in diabetic rats and 3T3-l1 adipocytes.  Diabetes. 1999;  48 1365-1371
  • 17 Duggirala R, Blangero J, Almasy L, Ayra R, Dyer TD, Williams KL, Leach RJ, O'Connell P, Stern MP. A major locus for fasting insulin concentrations and insulin resistance on chromosome 6q with strong pleiotropic effects on obesity-related phenotypes in nondiabetic Mexican Americans.  Am J Hum Genet. 2001;  68 1149-1164
  • 18 Temple JK, Gardner RJ, Robinson DO, Kilbirige MS, Fergusson AW, Baum JD, Barber JCK, James RS, Shield JPH. Further evidence for an imprinted gene for neonatal diabetes localized to chromosome 6q22-q23.  Hum Mol Genet. 1996;  5 1117-1121
  • 19 Goldfine ID, Maddux BA, Youngren JF, Frittitta L, Trischitta V, Dohm GL. Membrane glycoprotein PC-1 and insulin resistance.  Mol Cell Biochem. 1998;  182 177-184
  • 20 Goding JW, Terkeltaub R, Maurice M, Deterre P, Sali A, Belli SI. Ecto-phosphodiesterase/pyrophosphatase of lymphocytes and non-lymphoid cells: structure and function of the PC-1 family.  Immunol Rev. 1998;  161 11-26
  • 21 Terkeltaub RA. Inorganic pyrophosphate generation and disposition in pathophysiology.  Am J Physiol Cell Physiol. 2001;  281 C1-C11
  • 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 Frittitta L, Barata R, Spampinato D, DiPaola R, Pizuti A, Vigneri R, Trischitta V. The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance.  J Clin Endocrinol Metab. 2003;  86 5888-5891
  • 24 Hamaguchi K, Terao H, Kusuda Y, Yamashita T, Hazoury Bahles JA, Cruz LLM, Brugal LIV, Jongchong B, 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
  • 25 Kubaszek A, Pihlajamäki 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;  26 464-467
  • 26 Pizzuti A, Frittitta L, Argiolas A, Baratta R, Goldfine ID, Bozzali M, Ercolino T, Scarlato G, Iacoviello L, Vigneri R, Tassi V, Trischitta V. A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance.  Diabetes. 1999;  48 1881-1884
  • 27 Gonzales-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.  Obesity Research. 2003;  11 603-605
  • 28 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
  • 29 Laukkanen O, Pihlajymäki J, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto j, Uusitupa M, Laakso M. for the Finnish Diabetes Prevention Group . Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to type 2 diabetes.  Diabetologia. 2004;  47 871-877
  • 30 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
  • 31 Rasmussen SK, Urhammer SA, Pizzuti A, Echwald SM, Ekstrom CT, Hansen L, Hansen T, Borch-Johnsen K, Frittitta L, Trischita V, Pedersen O. 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
  • 32 Costanzo BV, Trischitta V, DiPaola 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
  • 33 Bollen M, Gijsbers R, Ceulemans H, Stalmans W, Stefan C. Nucleotide pyrophosphatases/phosphodiesterases on the move.  Crit Rev Biochem Mol Biol. 2000;  35 393-432
  • 34 Endler G, Mannhalter C, Sunder-Plassmann H, Schillinger M, Klimesch A, Exner M, Kapiotis S, Meier S, Kunz F, Raiger E, Huber K, Wagner O, Sunder-Plassmann R. The K121Q polymorphism in the plasma cell membrane glycoprotein 1 gene predisposes to early myocardial infarction.  J Mol Med. 2002;  80 791-795
  • 35 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.  Diabetes Care. 1997;  20 1183-1197
  • 36 De Fronzo RA. Lilly lecture 1987. The triumvirate: b-cell, muscle, liver. A collusion responsible for NIDDM.  Diabetes. 1988;  37 667-687
  • 37 Kahn BB, Flier JS. Obesity and insulin resistance.  J Clin Invest. 2000;  106 473-481
  • 38 Groop LC. The molecular genetics of non-insulin-dependent diabetes mellitus.  J Intern Med. 1997;  241 95-101
  • 39 Goldstein BJ. Insulin resistance as the core defect in type 2 diabetes mellitus.  Am J Cardiol. 2002;  90 3G-10G
  • 40 Hegele RA, Harris SB, Zinman B, Hanley AJ, Cao H. Absence of association of type 2 diabetes with CAPN 10 and PC-1 polymorphisms in Oji-Cree.  Diabetes Care. 2001;  24 1499
  • 41 Kubaszek A, Markkanen A, Eriksson JG, Forsen T, Osmond C, Barker JP, 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
  • 42 Abate N, Carulli L, Cabo-Chan A, 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
  • 43 Lalueza-Fox C, Calderon EL, Calafell F, Morera B, Bertanpetit J. MtDNA from extinct Tainos and the peopling of the Caribbean.  Ann Hum Genet. 2001;  65 137-151
  • 44 DeCosmo S, Trevisan R, Dalla Vestra M, Vedovato M, Argiolas A, Solini A, Saller A, Damone F, Tiengo A, Trischitta V, Fioretto P. PC-1 amino acid variant Q121 is associated with a lower glomerular filtration rate in type 2 diabetic patients with abnormal albumin excretion rates.  Diabetes Care. 2003;  26 2898-2902
  • 45 Marre M. A KQ121 variant in the PC-1gene and diabetic nephropathy: discrepant results between North and South Europe.  Nephrol Dial Transplant. 2002;  17 1546-1547

Correspondence

PD Dr. Ioanna Gouni-Berthold

Klinik II und Poliklinik für Innere Medizin·University of Cologne

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Phone: +49/221/478 40 70

Fax: +49/221/478 41 79

Email: i.berthold@uni-bonn.de

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