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Association of −394C>G and −420C>G polymorphisms in the RETN gene with T2DM and CHD and a new potential SNP might be exist in exon 3 of RETN gene in Chinese

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Abstract

Genetic variations of the human RETN gene are associated with metabolic phenotypes, including obesity, insulin sensitivity, diabetes, and coronary heart disease (CHD). There are few studies of two gene variants, −394C>G and −420C>G, in Chinese population. This study investigated the distribution of RETN gene, single nucleotide polymorphisms (SNPs), in Chinese Han population and the association of the polymorphisms with type 2 diabetes mellitus (T2DM) and CHD. In a population-based, case–control genetic association study, a total of 961 subjects were recruited from the community, including 318 T2DM patients, 273 CHD patients, and 370 unrelated healthy control individuals. Serum lipid levels were detected. Two SNPs of RETN gene, −394C>G and −420C>G, were genotyped by PCR-RFLP. Unknown Polymorphisms were screened with the technique of denaturing high performance liquid chromatography (DHPLC). The frequencies of RETN −394G allele in T2DM group, CHD group, and control group were 0.3066, 0.3555, and 0.3481, respectively, which are met with the Hardy–Weinberg equilibrium. There is a significant difference of the comparison of sex in T2DM group of RETN gene SNP-394C>G (P < 0.05). Compared with controls, there was no significant difference in the distribution of genotypes and allele frequencies of −394C>G polymorphic site in T2DM patients and CHD patients, respectively. No direct association was found between the −394C>G polymorphism and T2DM or CHD. The frequencies of RETN −420G allele in T2DM group, CHD group, and control group were 0.4009, 0.3725, and 0.3859, respectively, which are met with the Hardy–Weinberg equilibrium. The frequencies of RETN −420G allele in T2DM groups and control groups of Chinese population are significantly different from those in European population (0.40 vs. 0.27, 0.39 vs. 0.26) (P < 0.01). Compared with controls, there was no significant difference in distribution of genotypes and allele frequencies of −420C>G polymorphic site in T2DM patients and CHD patients, respectively. No direct association was found between the −420C>G polymorphism and T2DM or CHD. In addition, we found new potential SNP +593G>C in exon 3 of RETN gene using DHPLC. The RETN gene exhibits sex and ethnic differences. +593G>C of RETN gene might be a new potential SNP in exon 3 of RETN gene. Association between SNP −394C>G and −420C>G of RETN gene with T2DM and CHD in Chinese needs more exploration.

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References

  1. Steppan CM, Bailey ST, Bhat S et al (2001) The hormone RETN links obesity to diabetes. Nature 409:307–312. doi:10.1038/35053000

    Article  CAS  PubMed  Google Scholar 

  2. Ghosh S, Singh AK, Aruna B et al (2003) The genomic organization of mouse RETN reveals major differences from the human RETN: functional implications. Gene 13:27–34. doi:10.1016/S0378-1119(02)01213-1

    Article  Google Scholar 

  3. Burnett MS, Lee CW, Kinnaird TD et al (2005) The potential role of RETN in atherogenesis. Atherosclerosis 182:241–248. doi:10.1016/j.atherosclerosis.2005.02.014

    Article  CAS  PubMed  Google Scholar 

  4. Burnett MS, Devaney JM, Adenika RJ et al (2006) Cross-sectional associations of resistin, coronary heart disease, and insulin resistance. J Clin Endocrinol Metab 91:64–68. doi:10.1210/jc.2005-1653

    Article  CAS  PubMed  Google Scholar 

  5. Wang H, Chu WS, Hemphill C et al (2002) Human RETN gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in caucasians. J Clin Endocrinol Metab 87:2520–2524. doi:10.1210/jc.87.6.2520

    Article  CAS  PubMed  Google Scholar 

  6. Steppan CM, Brown EJ, Wright CM et al (2001) A family of tissue-specific RETN-like molecules. Proc Natl Acad Sci USA 98:502–506. doi:10.1073/pnas.98.2.502

    Article  CAS  PubMed  Google Scholar 

  7. Reilly MP, Lehrke M, Wolfe ML et al (2005) RETN is an inflammatory marker of atherosclerosis in humans. Circulation 111:932–939. doi:10.1161/01.CIR.0000155620.10387.43

    Article  CAS  PubMed  Google Scholar 

  8. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285:2486–2497. doi:10.1001/jama.285.19.2486

    Article  Google Scholar 

  9. Reaven GM (1988) Banting lecture: role of insulin resistance in human disease. Diabetes 37:1595–1607. doi:10.2337/diabetes.37.12.1595

    Article  CAS  PubMed  Google Scholar 

  10. Ross R (1999) Atherosclerosis: an inflammatory disease. N Engl J Med 340:115–126. doi:10.1056/NEJM199901143400207

    Article  CAS  PubMed  Google Scholar 

  11. Festa A, D Agostino R Jr, Howard G et al (2000) Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102:42–47

    CAS  PubMed  Google Scholar 

  12. Conneely KN, Silander K, Scott LJ et al (2004) Variation in the RETN gene is associated with obesity and insulin-related phenotypes in Finish subjects. Diabetologia 47:1782–1788. doi:10.1007/s00125-004-1537-x

    Article  CAS  PubMed  Google Scholar 

  13. Cho YM, Youn BS, Chung SS et al (2004) Common genetic polymorphisms in the promoter of RETN gene are major determinants of plasma RETN concentrations in humans. Diabetologia 47:559–565

    CAS  PubMed  Google Scholar 

  14. Duman BS, Cagatay P, Hatemi H et al (2007) Association of resistin gene 3′-untranslated region EX4-44G→A polymorphism with obesity- and insulin-related phenotypes in turkish type 2 diabetes patients. Rev Diabet Stud 4:49–55. doi:10.1900/RDS.2007.4.49

    Article  PubMed  Google Scholar 

  15. Krízová J, Dolinková M, Lacinová Z et al (2007) Adiponectin and resistin gene polymorphisms in patients with anorexia nervosa and obesity and its influence on metabolic phenotype. Physiol Res 57:539–546

    PubMed  Google Scholar 

  16. Bouchard L, Weisnagel SJ, Engert JC et al (2004) Human resistin gene polymorphism is associated with visceral obesity and fasting and oral glucose stimulated C-peptide in the Québec Family Study. J Endocrinol Invest 27:1003–1009

    CAS  PubMed  Google Scholar 

  17. Pfützner A, Langenfeld M, Kunt T et al (2003) Evaluation of human resistin assays with serum from patients with type 2 diabetes and different degrees of insulin resistance. Clin Lab (Zaragoza) 49:571–576

    Google Scholar 

  18. Steppan CM, Lazar MA (2002) Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 13:18–23. doi:10.1016/S1043-2760(01)00522-7 Review

    Article  CAS  PubMed  Google Scholar 

  19. Savage DB, Sewter CP, Klenk ES et al (2001) RETN/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 50:2199–2202. doi:10.2337/diabetes.50.10.2199

    Article  CAS  PubMed  Google Scholar 

  20. Yang RZ, Huang Q, Xu A et al (2003) Comparative studies of RETN expression and phylogenomics in human and mouse. Biochem Biophys Res Commun 310:927–935. doi:10.1016/j.bbrc.2003.09.093

    Article  CAS  PubMed  Google Scholar 

  21. Patel L, Buckels AC, Kinghorn IJ et al (2003) RETN is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 300:472–476. doi:10.1016/S0006-291X(02)02841-3

    Article  CAS  PubMed  Google Scholar 

  22. Plutzky J (2001) Inflammatory pathways in atherosclerosis and acute coronary syndromes. Am J Cardiol 88:10K–15K. doi:10.1016/S0002-9149(01)01924-5

    Article  CAS  PubMed  Google Scholar 

  23. Lehrke M, Reilly MP, Millington SC et al (2004) An inflammatory cascade leading to hyperRETNemia in humans. PLoS Med 1:e45. doi:10.1371/journal.pmed.0010045

    Article  PubMed  Google Scholar 

  24. Bokarewa M, Nagaev I, Dahlberg L et al (2005) RETN, an adipokine with potent proinflammatory properties. J Immunol 174:5789–5795

    CAS  PubMed  Google Scholar 

  25. Youn BS, Yu KY, Park HJ et al (2004) Plasma RETN concentrations measured by enzyme-linked immunosorbent assay using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 89:150–156. doi:10.1210/jc.2003-031121

    Article  CAS  PubMed  Google Scholar 

  26. Fujinami A, Obayashi H, Ohta K et al (2004) Enzyme-linked immunosorbent assay for circulating human RETN: RETN concentrations in normal subjects and patients with type 2 diabetes. Clin Chim Acta 339:57–63. doi:10.1016/j.cccn.2003.09.009

    Article  CAS  PubMed  Google Scholar 

  27. Zhang JL, Qin YW, Zheng X et al (2003) Serum RETN level in essential hypertension patients with different glucose tolerance. Diabet Med 20:828–831. doi:10.1046/j.1464-5491.2003.01057.x

    Article  CAS  PubMed  Google Scholar 

  28. McTernan PG, Fisher FM, Valsamakis G et al (2003) RETN and type 2 diabetes: regulation of RETN expression by insulin and rosiglitazone and the effects of recombinant RETN on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 88:6098–6106. doi:10.1210/jc.2003-030898

    Article  CAS  PubMed  Google Scholar 

  29. Al-Daghri N, Chetty R, McTernan PG et al (2005) Serum RETN is associated with C-reactive protein and LDL cholesterol in type 2 diabetes and coronary artery disease in a Saudi population. Cardiovasc Diabetol 4:10. doi:10.1186/1475-2840-4-10

    Article  CAS  PubMed  Google Scholar 

  30. Shetty GK, Economides PA, Horton ES et al (2004) Circulating adiponectin and RETN levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 27:2450–2457. doi:10.2337/diacare.27.10.2450

    Article  CAS  PubMed  Google Scholar 

  31. Jung HS, Park KH, Cho YM et al (2006) RETN is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovasc Res 69:76–85. doi:10.1016/j.cardiores.2005.09.015

    Article  CAS  PubMed  Google Scholar 

  32. Satoh H, Nguyen MT, Miles PD et al (2004) Adenovirus-mediated chronic “hyper-RETNemia” leads to in vivo insulin resistance in normal rats. J Clin Invest 114:224–231

    CAS  PubMed  Google Scholar 

  33. Aramaki M, Udaka T, Torii C et al (2006) Screening for CHARGE syndrome mutations in the CHD7 gene using denaturing high-performance liquid chromatography. Genet Test 10:244–251. doi:10.1089/gte.2006.10.244

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 30671155) and the Chinese High Tech Programs (863) from the Ministry of Science and Technology (No. 2002BA711A08). We gratefully acknowledge the medical genetics laboratory in Sichuan University for technical support and the endocrinal department in West China Hospital for assistance.

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Authors and Affiliations

  1. Department of Cell Biology and Genetics, and Center of Neuroscience, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, China

    Shuguang Chi, Cailian Lan, Hekun Liu, Xizhen Wang, Xuexiang Chen & Suyun Chen

  2. Department of Medical Genetics, West China Hospital, Sichuan University, and Division of Human Morbid Genomics, State Key Laboratory of Biotherapy of Human Diseases, Chengdu, China

    Sizhong Zhang & Wei Zhang

  3. Department of Hematology, Union Hospital, Fujian Medical University, Fuzhou, China

    Yuanzhong Chen

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  1. Shuguang Chi
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  2. Cailian Lan
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Correspondence to Hekun Liu.

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Chi, S., Lan, C., Zhang, S. et al. Association of −394C>G and −420C>G polymorphisms in the RETN gene with T2DM and CHD and a new potential SNP might be exist in exon 3 of RETN gene in Chinese. Mol Cell Biochem 330, 31–38 (2009). https://doi.org/10.1007/s11010-009-0097-2

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