Association of K121Q Polymorphism in Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 with Clinical Characteristics of Metabolic Syndrom

Abstract

Purpose: This study aimed to investigate the relationships between K121Q polymorphism of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and clinical characteristics of metabolic syndrome (MS) in northern Han Chinese.

Materials and Methods: A total of 209 MS patients and 248 healthy controls of Han ethnic group in northern China were enrolled in this study. Various clinical parameters of these participants were firstly collected and compared, including age, sex, body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressures (SBP/DBP), fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance index (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density and low-density lipoprotein cholesterol (LDL-C/HDL-C). Then K121Q polymorphism of ENPP1 was determined by PCR and restriction enzyme digestion, and its relations with related clinical parameters were finally analyzed.

Results: When compared with healthy controls, the age, BMI, WC, SBP, DBP, FPG, FINS, HOMA-IR, TC, TG and LDL-C were all significantly increased in MS patients (P<0.001). The allele frequencies of K and Q alleles in ENPP1 were 90.19% and 9.81% in MS patients, and 91.73% and 8.27% in healthy controls, respectively. Besides, only BMI and WC were significantly increased in MS patients carrying Q alleles (P<0.001), while no significant relations were found between K121Q polymorphism and other clinical parameters in either MS patients or healthy controls.

Conclusion: The K121Q polymorphism of ENPP1 showed no direct correlation with MS, although it showed some correlation with BMI and WC in MS patients.

Key words

ectonucleotide pyrophosphatase/phosphodiesterase 1 - polymorphism - metabolic syndrome - obesity

• References

• 1 Pan WH, Yeh WT, Weng LC. Epidemiology of metabolic syndrome in Asia. Asia Pac J Clin Nutr 2008; 17 (Suppl. 01) 37-42
• 2 Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014; 2014: 943162
• 3 Pimenta AM, Toledo E, Rodriguez-Diez MC et al. Dietary indexes, food patterns and incidence of metabolic syndrome in a Mediterranean cohort: The SUN project. Clin Nutr 2015; 34: 508-514
• 4 Gu D, Reynolds K, Wu X et al. Prevalence of the metabolic syndrome and overweight among adults in China. Lancet 2005; 365: 1398-1405
• 5 Alberti KG, Zimmet P, Shaw J. The metabolic syndrome – a new worldwide definition. Lancet 2005; 366: 1059-1062
• 6 Pollex RL, Hegele RA. Genetic determinants of the metabolic syndrome. Nat Clin Pract Cardiovasc Med 2006; 3: 482-489
• 7 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
• 8 Dong H, Maddux BA, Altomonte J et al. Increased hepatic levels of the insulin receptor inhibitor, PC-1/NPP1, induce insulin resistance and glucose intolerance. Diabetes 2005; 54: 367-372
• 9 Costanzo BV, Trischitta V, Di Paola R et al. 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
• 10 Frittitta L, Baratta R, Spampinato D et al. The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance. J Clin Endocrinol Metab 2001; 86: 5888-5891
• 11 Li YY. ENPP1 K121Q polymorphism and type 2 diabetes mellitus in the Chinese population: a meta-analysis including 11,855 subjects. Metabolism 2012; 61: 625-633
• 12 Lee JE, Choi YK, Seo HA 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
• 13 Saberi H, Mohammadtaghvaei N, Gulkho S et al. The ENPP1 K121Q polymorphism is not associated with type 2 diabetes and related metabolic traits in an Iranian population. Mol Cell Biochem 2011; 350: 113-118
• 14 Weedon MN, Shields B, Hitman G 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: 3175-3179
• 15 Lyon HN, Florez JC, Bersaglieri T et al. Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity. Diabetes 2006; 55: 3180-3184
• 16 Zhao T, Liu Z, Zhang 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: 12-16
• 17 Ford ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care 2005; 28: 2745-2749
• 18 Rasmussen SK, Urhammer SA, Pizzuti A 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, Zabena C, Martinez-Larrad MT et al. Association of ENPP1 (PC-1) K121Q polymorphism with obesity-related parameters in subjects with metabolic syndrome. Clin Endocrinol (Oxf) 2008; 68: 724-729
• 20 Bassi N, Karagodin I, Wang S et al. Lifestyle modification for metabolic syndrome: a systematic review. Am J Med 2014; 127: 1242. e1-1242.e10
• 21 Bacci S, De Cosmo S, Prudente S et al. ENPP1 gene, insulin resistance and related clinical outcomes. Curr Opin Clin Nutr Metab Care 2007; 10: 403-409
• 22 Mcateer JB, Prudente S, Bacci S 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: 1125-1130
• 23 Pizzuti A, Frittitta L, Argiolas A 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
• 24 Grarup N, Urhammer S, Ek J 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: 2097-2104
• 25 González-Sánchez JL, Zabena C, Martínez-Larrad MT, Martínez-Calatrava MJ, Pérez-Barba M, Serrano-Ríos M. Association of ENPP1 (PC-1) K121Q polymorphism with obesity-related parameters in subjects with metabolic syndrome. Clinical endocrinology 2008; 68: 724-729
• 26 Meyre D, Bouatia-Naji N, Tounian A 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
• 27 Grarup N, Urhammer SA, Ek J 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: 2097-2104
• 28 Seo HJ, Kim SG, Kwon OJ. The K121Q polymorphism in ENPP1 (PC-1) is not associated with type 2 diabetes or obesity in Korean male workers. J Korean Med Sci 2008; 23: 459-464
• 29 Chen MP, Chung FM, Chang DM 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
• 30 Kubaszek A, Pihlajamaki J, Karhapaa P et al. The K121Q polymorphism of the PC-1 gene is associated with insulin resistance but not with dyslipidemia. Diabetes Care 2003; 26: 464-467
• 31 Gonzalez-Sanchez JL, Martinez-Larrad MT, Fernandez-Perez C et al. K121Q PC-1 gene polymorphism is not associated with insulin resistance in a Spanish population. Obes Res 2003; 11: 603-605
• 32 Pizzuti A, Frittitta L, Argiolas A 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
• 33 Keshavarz P, Inoue H, Sakamoto Y 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: 559-566