Biochemical Genetics

, Volume 50, Issue 7–8, pp 549–559 | Cite as

An Interleukin-10 Gene Promoter Polymorphism (−592A/C) Associated with Type 2 Diabetes: A North Indian Study

  • Madhukar Saxena
  • C. G. Agrawal
  • Hemant Kumar Bid
  • Monisha Banerjee
Article

Abstract

In this first report on the association of an IL-10 promoter polymorphism with type 2 diabetes mellitus in a North Indian population, the −592A/C SNP (rs1800872) was genotyped by PCR–RFLP and the IL-10 level measured using ELISA. Although no significant difference was observed in the genotypic frequencies (P = 0.657), diabetes patients carried a significantly higher number of A alleles at the −592 position, 25.6% (P < 0.001, odds ratio 0.887, 95% CI 0.670–1.184). Significant correlations were detected in postprandial glucose levels of CC-genotype patients and controls (P = 0.025), age and waist–hip ratio of CA patients and controls (P ≤ 0.001), and fasting glucose (P = 0.045) and low-density lipoprotein (P = 0.049) in all patients and controls. The serum IL-10 level was significantly higher in patients than in controls (P = 0.033). The polymorphism was significantly associated with disease incidence and its biochemical manifestations.

Keywords

SNP Type 2 diabetes mellitus Interleukin-10 North Indian population ELISA PCR–RFLP 

References

  1. American Diabetes Association (2010) Screening for type 2 diabetes. Diabetes Care 33:S1CrossRefGoogle Scholar
  2. Chang YH, Huang CN, Wu CY, Shiau MY (2005) Association of interleukin-10 A−592C and T−819C polymorphisms with type 2 diabetes mellitus. Hum Immunol 66:1258–1263PubMedCrossRefGoogle Scholar
  3. D’Alfonso S, Rampi M, Bocchio D, Colombo G, Scorza-Smeraldi R, Momigliano-Richardi P (2000) Systemic lupus erythematosus candidate genes in the Italian population: evidence for a significant association with interleukin-10. Arthritis Rheum 43:120–128PubMedCrossRefGoogle Scholar
  4. Edwards-Smith CJ, Jonsson JR, Purdie DM, Bansal A, Shorthouse C, Powell EE (1999) Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon α. Hepatology 30:526–530PubMedCrossRefGoogle Scholar
  5. Eskdale J, Gallagher G, Verweij CL, Keijsers V, Westendrotp RG, Huizinga TW (1998) Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA 95:9465–9470PubMedCrossRefGoogle Scholar
  6. Forte GI, Pilato G, Vaccarino L, Sanacore M, Candore G, Romano GC, Testa R, Franceschi C, Capri M, Marra M, Bonfigli AR, Caruso C, Scola L, Lio D (2010) Risk profile in type 2 diabetes (metabolic syndrome): integration of IL-10 polymorphisms and laboratory parameters to identify vascular damage related complications. Curr Pharm Des 16:898–903PubMedCrossRefGoogle Scholar
  7. Hong EG, Ko HJ, Cho YR, Kim HJ, Ma Z, Yu TY, Friedline RH, Kurt-Jones E, Finberg R, Fischer MA, Granger EL, Norbury CC, Hauschka SD, Philbrick WM, Lee CG, Elias JA, Kim JK (2009) Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes 58:2525–2535PubMedCrossRefGoogle Scholar
  8. Ide A, Kawasaki E, Abiru N, Sun F, Takahashi R, Kuwahara H, Fujita N, Kita A, Oshima K, Sakamaki H, Uotani S, Yamasaki H, Yamaguchi Y, Eguchi K (2002) Genetic association between interleukin-10 gene promoter region polymorphisms and type 1 diabetes age-at-onset. Hum Immunol 63:690–695PubMedCrossRefGoogle Scholar
  9. Kung WJ, Lin CC, Liu SH, Chaung HC (2010) Association of interleukin-10 polymorphism with cytokines in type 2 diabetes nephropathy. Diabetes Technol Ther 12:809–813PubMedCrossRefGoogle Scholar
  10. Lu MY, Lakkakula BVKS, Liao YC, Tsai PC, Yang YH, Juo SHH (2011) Lack of association between the IL-10 gene polymorphisms and features of the metabolic syndrome. J Invest Med 59:27–267Google Scholar
  11. Malecka-Tendera E, Erhardt E, Molnar D (2005) Type 2 diabetes mellitus in European children and adolescents. Acta Paediatr 94:534–546CrossRefGoogle Scholar
  12. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMedCrossRefGoogle Scholar
  13. Mohan V, Sandeep S, Deepa R, Shah B, Varghese C (2007) Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res 125:217–230PubMedGoogle Scholar
  14. Mohebbatikaljahi H, Menevse S, Yetkin I, Demirci H (2009) Study of interleukin-10 promoter region polymorphisms (−1082A/G, −819T/C and −592A/C) in type 1 diabetes mellitus in Turkish population. J Genet 88:245–248PubMedCrossRefGoogle Scholar
  15. Moritani M, Yoshimoto K, Tashiro F, Hashimoto C, Miyazaki J, Ii S, Kudo E, Iwahana H, Hayashi Y, Sano T, Itakura M (1994) Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes in non-obese diabetic mice. Int Immunol 6:1927–1936PubMedCrossRefGoogle Scholar
  16. Mosmann TR (1994) Properties and functions of interleukin-10. Adv Immunol 56:1–26PubMedCrossRefGoogle Scholar
  17. Opal SM, DePalo VA (2000) Anti-inflammatory cytokines. Chest 117:1162–1172PubMedCrossRefGoogle Scholar
  18. Pakala SV, Kurrer MO, Katz JD (1997) T helper 2 (Th2) cells induce acute pancreatitis and diabetes in immune-compromised non-obese diabetic (NOD) mice. J Exp Med 186:299–306PubMedCrossRefGoogle Scholar
  19. Pennline KJ, Roque-Gaffney E, Monahan M (1994) Recombinant human IL-10 prevents the onset of diabetes in the non-obese diabetic mouse. Clin Immunol Immunopathol 71:169–175PubMedCrossRefGoogle Scholar
  20. Saxena M, Banerjee M (2008) Diabetes: history, prevalence, insulin action and associated genes. J Appl Biosci 34:139–151Google Scholar
  21. Scarpelli D, Cardellini M, Andreozzi F, Laratta E, Hribal ML, Marini MA, Tassi V, Lauro R, Perticone F, Sesti G (2006) Variants of the interleukin-10 promoter gene are associated with obesity and insulin resistance but not type 2 diabetes in Caucasian Italian subjects. Diabetes 55:1529–1533PubMedCrossRefGoogle Scholar
  22. Slobedman B, Barry PA, Spencer JV, Avdic S, Abendroth A (2009) Virus-encoded homologs of cellular interleukin-10 and their control of host immune function. J Virol 83:9618–9629PubMedCrossRefGoogle Scholar
  23. Tan KCB, Chow WS, Tam S, Bucala R, Betteridge J (2004) Association between acute-phase reactants and advanced glycation end products in type 2 diabetes. Diabetes Care 27:223–228PubMedCrossRefGoogle Scholar
  24. Tfayli H, Arslanian S (2009) Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon. Arq Bras Endocrinol Metab 53:165–174CrossRefGoogle Scholar
  25. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1–8PubMedCrossRefGoogle Scholar
  26. van Exel E, Gussekloo J, de Craen ALM, Bootsma-van der Wiel A, Frölich M, Westendorp GJ (2002) Inflammation and stroke: the Leiden 85-plus study. Stroke 33:1135–1338PubMedCrossRefGoogle Scholar
  27. Weger M, Steinbrugger I, El-Shabrawi Y, Wegscheider BJ, Weger W, Renner W, Schmut O, Hass A (2007) Haplotype-tagging interleukin-10 promoter polymorphism is associated with reduced risk of retinal artery occlusion. Mol Vis 13:549–552PubMedGoogle Scholar
  28. Wogensen L, Lee MS, Sarvetnick N (1994) Production of interleukin 10 by islet cells accelerates immune-mediated destruction of b cells in non-obese diabetic mice. J Exp Med 179:1379–1384PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Madhukar Saxena
    • 1
  • C. G. Agrawal
    • 2
  • Hemant Kumar Bid
    • 3
  • Monisha Banerjee
    • 1
  1. 1.Molecular and Human Genetics Laboratory, Department of ZoologyUniversity of LucknowLucknowIndia
  2. 2.Department of MedicineChhatrapati Shahuji Maharaj Medical UniversityLucknowIndia
  3. 3.Peter Houghton Lab, Center for Childhood CancerResearch Institute at Nationwide Children’s HospitalColumbusUSA

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