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Fruit and vegetable intake modifies the associations between suppressor of cytokine signaling 3 genetic variants and type 2 diabetes

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Abstract

Purpose

Type 2 diabetes is a complex disease determined by variable genes and environmental factors. The study was designed to investigate the effect of interactions of four polymorphisms of suppressor of cytokine signaling 3 (SOCS3) with fruit and vegetable (F&V) intake on type 2 diabetes in a rural population of China.

Methods

A total of 4411 participants from the rural areas of Henan, China were included in the study. Multivariate logistic regression and restricted cubic splines were used to estimate the associations between polymorphisms and risk allele score of SOCS3 and type 2 diabetes in different groups. Haplotype analysis was conducted to examine the effects of linkage inheritance at these four loci on type 2 diabetes.

Results

Three of the four polymorphisms showed significant associations with type 2 diabetes in the less F&V intake group after adjusting the covariates, the odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were 1.24 (1.08–1.41) for rs4969168, 1.16 (1.02–1.32) for rs9892622, and 1.21 (1.06–1.39) for rs9914220. No significant association was detected in the more F&V intake group. The obvious dose–response relationship between the risk allele score and type 2 diabetes was also noted only in the less F&V intake group.

Conclusions

Variants of SOCS3 gene were associated with type 2 diabetes and the associations could be modified by the F&V intake.

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References

  1. Da Rocha FJ, Ogurtsova K, Linnenkamp U et al (2016) IDF Diabetes Atlas estimates of 2014 global health expenditures on diabetes. Diabetes Res Clin Pract 117:48–54. https://doi.org/10.1016/j.diabres.2016.04.016

    Article  Google Scholar 

  2. Yang W, Lu J, Weng J et al (2010) China National Diabetes And Metabolic Disorders study group. prevalence of diabetes among men and women in China. N Engl J Med 362:1090–1101. https://doi.org/10.1056/NEJMoa0908292

    Article  CAS  PubMed  Google Scholar 

  3. International Diabetes Federation (2018) IDF diabetes atlas-8th edition. www.diabetesatlas.org/. Accessed 18 Oct 2018

  4. Cooper AJ, Forouhi NG, Ye Z et al (2012) Fruit and vegetable intake and type2 diabetes: EPIC-InterAct prospective study and meta-analysis. Eur J Clin Nutr 66:1082–1092. https://doi.org/10.1038/ejcn.2012.85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Siegel KR, Bullard KM, Imperatore G et al (2018) Prevalence of major behavioral risk factors for type 2 diabetes. Diabetes Care 41:1032–1039. https://doi.org/10.2337/dc17-1775

    Article  PubMed  PubMed Central  Google Scholar 

  6. Talbert ME, Langefeld CD, Ziegler J et al (2009) Polymorphisms near SOCS3 are associated with obesity and glucose homeostasis traits in Hispanic Americans from the Insulin Resistance Atherosclerosis Family Study. Hum Genet 125:153–162. https://doi.org/10.1007/s00439-008-0608-3

    Article  CAS  PubMed  Google Scholar 

  7. Mahony R, Ahmed S, Diskin C, Stevenson NJ (2016) SOCS3 revisited: a broad regulator of disease, now ready for therapeutic use? Cell Mol Life Sci 73:3323–3336. https://doi.org/10.1007/s00018-016-2234-x

    Article  CAS  PubMed  Google Scholar 

  8. Emanuelli B, Peraldi P, Filloux C et al (2001) SOCS-3 inhibits insulin signaling and is up-regulated in response to tumor necrosis factor-α in the adipose tissue of obese mice. J Biol Chem 276:47944–47949. https://doi.org/10.1074/jbc.M104602200

    Article  CAS  PubMed  Google Scholar 

  9. Jamshidi Y, Snieder H, Wang X, Spector TD, Carter ND, O'Dell SD (2006) Common polymorphisms in SOCS3 are not associated with body weight, insulin sensitivity or lipid profile in normal female twins. Diabetologia 49:306–310. https://doi.org/10.1007/s00125-005-0093-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fischer-Rosinsky A, Fisher E, Kovacs P et al (2008) Lack of association between the tagging SNP A+930RG of SOCS3 and type 2 diabetes mellitus: meta-analysis of four independent study populations. PLoS ONE 3:e3852. https://doi.org/10.1371/journal.pone.0003852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tang W, Zou JJ, Chen XF et al (2011) Association of two polymorphisms within and near SOCS3 gene with obesity in three nationalities in Xinjiang province of China. Acta Pharmacol Sin 32:1381–1386. https://doi.org/10.1038/aps.2011.84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li P, Tiwari HK, Lin WY et al (2014) Genetic association analysis of 30 genes related to obesity in a European American population. Int J Obes 38:724–729. https://doi.org/10.1038/ijo.2013.140

    Article  CAS  Google Scholar 

  13. Zheng YY, Wang LF, Fan XH et al (2013) Association of suppressor of cytokine signalling 3 polymorphisms with insulin resistance in patients with chronic hepatitis C. J Viral Hepat 20:273–280. https://doi.org/10.1111/j.1365-2893.2012.01644.x

    Article  PubMed  Google Scholar 

  14. Liu XT, Mao ZX, Li YQ et al (2019) The Henan Rural Cohort: a prospective study of chronic non-communicable diseases. Int J Epidemiol pii:dyz039. https://doi.org/10.1093/ije/dyz039

    Article  Google Scholar 

  15. Perloff D, Grim C, Flack J et al (1993) Human blood pressure determination by sphygmomanometry. Circulation 88:2460–2470

    Article  CAS  PubMed  Google Scholar 

  16. Fan M, Lyu J, He P (2014) Chinese guidelines for data processing and analysis concerning the International Physical Activity Questionnaire. Zhonghua Liu Xing Bing Xue Za Zhi 35:961–964

    PubMed  Google Scholar 

  17. Yang YX, Zhang HM (2016) The dietary guidelines for Chinese residents (2016). Acta Nutr Sin 38:209–217. https://doi.org/10.13325/j.cnki.acta.nutr.sin.2016.03.002

    Article  Google Scholar 

  18. American Diabetes Association (2009) Diagnosis and classification of diabetes mellitus. Diabetes Care 32:S62–S67. https://doi.org/10.2337/dc09-S062

    Article  PubMed Central  Google Scholar 

  19. Desquilbet L, Mariotti F (2010) Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 29:1037–1057. https://doi.org/10.1002/sim.3841

    Article  PubMed  Google Scholar 

  20. Lee DH, Keum N, Hu FB et al (2018) Comparison of the association of predicted fat mass, body mass index, and other obesity indicators with type 2 diabetes risk: two large prospective studies in US men and women. Eur J Epidemiol 33:1113–1123. https://doi.org/10.1007/s10654-018-0433-5

    Article  CAS  PubMed  Google Scholar 

  21. Boeing H, Bechthold A, Bub A et al (2012) Critical review: vegetables and fruit in the prevention of chronic diseases. Nur J Nutr 51:637–663. https://doi.org/10.1007/s00394-012-0380-y

    Article  CAS  Google Scholar 

  22. World Health Organization (2003) Diet, nutrition and the prevention of chronic diseases. Report of a Joint WHO/FAO Expert Consulation, Geneva, https://whqlibdoc.who.int/trs/WHO_TRS_916.pdf?ua=1. Accessed 26 Oct 2019

  23. Nilsson E, Jansson PA, Perfilyev A et al (2014) Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes 63:2962–2976. https://doi.org/10.2337/db13-1459

    Article  PubMed  Google Scholar 

  24. Lontchi-Yimagou E, Sobngwi E, Matsha TE, Kengne AP (2013) Diabetes mellitus and inflammation. Curr Diabetes Rep 13:435–444. https://doi.org/10.1007/s11892-013-0375-y

    Article  CAS  Google Scholar 

  25. Mozaffarian D (2016) Dietary and policy priorities for cardiovascular disease, diabetes, and obesity a comprehensive review. Circulation 133:187–225. https://doi.org/10.1161/CIRCULATIONAHA.115.018585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R (2005) Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 111:1448–1454. https://doi.org/10.1161/01.CIR.0000158483.13093.9D

    Article  PubMed  Google Scholar 

  27. Ghanim H, Abuaysheh S, Sia CL et al (2009) Increase in plasma endotoxin concentrations and the expression of toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: Implications for insulin resistance. Diabetes Care 32:2281–2287. https://doi.org/10.2337/dc09-0979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Deopurkar R, Ghanim H, Friedman J et al (2010) Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes Care 33:991–997. https://doi.org/10.2337/dc09-1630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sass G, Shembade ND, Tiegs G (2005) Tumour necrosis factor alpha (TNF)-TNF receptor 1-inducible cytoprotective proteins in the mouse liver: relevance of suppressors of cytokine signalling. Biochem J 385:537–544. https://doi.org/10.1042/BJ20040279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Stevenson NJ, Addley MR, Ryan EJ (2009) CCL11 blocks IL-4 and GM-CSF signaling in hematopoietic cells and hinders dendritic cell differentiation via suppressor of cytokine signaling expression. J Leukoc Biol 85:289–297. https://doi.org/10.1189/jlb.0708394

    Article  CAS  PubMed  Google Scholar 

  31. Darnell JE, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extra cellular signalin proteins. Science 264:1415–1421. https://doi.org/10.1126/science.8197455

    Article  CAS  PubMed  Google Scholar 

  32. O'Shea JJ, Notarangelo LD, Johnston JA, Candotti F (1997) Advances in the understanding of cytokine signal transduction: the role of Jaks and STATs in immunoregulation and the pathogenesis of immunodeficiency. J Clin Immunol 17:431–447

    Article  CAS  PubMed  Google Scholar 

  33. Starr R, Willson TA, Viney EM et al (1997) A family of cytokine-inducible inhibitors of signalling. Nature 387:917–921

    Article  CAS  PubMed  Google Scholar 

  34. Hilton DJ, Richardson RT, Alexander WS et al (1998) Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc Natl Acad Sci USA 95:114–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Piessevaux J, Lavens D, Peelman F, Tavernier J (2008) The many faces of the SOCS box. Cytokine Growth Factor Rev 19:371–381. https://doi.org/10.1016/j.cytogfr.2008.08.006

    Article  CAS  PubMed  Google Scholar 

  36. Tamiya T, Kashiwagi I, Takahashi R, Yasukawa H, Yoshimura A (2011) Suppressors of cytokine signaling (SOCS) proteins and JAK/STAT pathways: regulation of T-cell inflammation by SOCS1 and SOCS3. Arterioscler Thromb Vasc Biol 31:980–985. https://doi.org/10.1161/ATVBAHA.110.207464

    Article  CAS  PubMed  Google Scholar 

  37. White MF (1998) The IRS-signalling system: a network of docking proteins that mediate insulin action. Mol Cell Biochem 182:3–11

    Article  CAS  PubMed  Google Scholar 

  38. Emanuelli B, Peraldi P, Filloux C, Sawka-Verhelle D, Hilton D, Van Obberghen E (2000) SOCS-3 is an insulin-induced negative regulator of insulin signaling. J Biol Chem 275:15958–15991. https://doi.org/10.1074/jbc.275.21.15985

    Article  Google Scholar 

  39. Shi H, Cave B, Inouye K, Bjørbaek C, Flier JS (2006) Overexpression of suppressor of cytokine signaling 3 in adipose tissue causes local but not systemic insulin resistance. Diabetes 55:699–707. https://doi.org/10.2337/diabetes.55.03.06.db05-0841

    Article  CAS  PubMed  Google Scholar 

  40. Heynsfield SB, Greenberg AS, Fujioka K et al (1999) Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose escalation trial. JAMA 282:1568–1575. https://doi.org/10.1001/jama.282.16.1568

    Article  Google Scholar 

  41. Babon JJ, Kershaw NJ, Murphy JM et al (2012) Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity. Immunity 36:239–250. https://doi.org/10.1016/j.immuni.2011.12.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Babon JJ, Nicola NA (2012) The biology and mechanism of action of suppressor of cytokine signaling 3. Growth Factors 30:207–219. https://doi.org/10.3109/08977194.2012.687375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cooper AJ, Sharp SJ, Lentjes MA et al (2012) A prospective study of the association between quantity and variety of fruit and vegetable intake and incident type 2 diabetes. Diabetes Care 35:1293–1300. https://doi.org/10.2337/dc11-2388

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ghanim H, Sia CL, Upadhyay M et al (2010) Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and toll-like receptor expression. Am J Clin Nutr 91:940–949. https://doi.org/10.3945/ajcn.2009.28584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sur I, Tuupanen S, Whitington T, Aaltonen LA, Taipale J (2013) Lessons from functional analysis of genome-wide association studies. Cancer Res 73:4180–4184. https://doi.org/10.1158/0008-5472.CAN-13-0789

    Article  CAS  PubMed  Google Scholar 

  46. Oldridge DA, Wood AC, Weichert-Leahey N et al (2015) Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature 528:418–421. https://doi.org/10.1038/nature15540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Melton C, Reuter JA, Spacek DV, Snyder M (2015) Recurrent somatic mutations in regulatory regions of human cancer genomes. Nat Genet 47:710–716. https://doi.org/10.1038/ng.3332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China [Grant NO: 81602925, 81573243, U1304821], Foundation of National Key Program of Research and Development of China [Grant NO: 2016YFC0900803], Henan Provincial Science Fund for Distinguished Young Scholars [Grant NO: 164100510021], Science and Technology Innovation Talents Support Plan of Henan Province Colleges and Universities [Grant NO: 14HASTIT035], and High-level Personnel Special Support Project of Zhengzhou University [Grant NO: ZDGD13001]. The study sponsor was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.

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Authors

Contributions

CJW and YQL were responsible for the conception and design of the study. XLQ, XTL, CJW, and YQL were responsible for recruitment, cohort management, and experiment. XLQ and XTL were responsible for analyzing the data and the integrity and accuracy of the information. XLQ, XTL, ZXM, TA, XKD, RQT, YW, XL, ZCL, and DQ were responsible for the reagents/materials/analysis tools. XLQ, XTL, TA, CJW, and YQL were responsible for drafting and revising the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Chongjian Wang or Yuqian Li.

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Qian, X., Liu, X., Mao, Z. et al. Fruit and vegetable intake modifies the associations between suppressor of cytokine signaling 3 genetic variants and type 2 diabetes. Eur J Nutr 59, 3441–3449 (2020). https://doi.org/10.1007/s00394-020-02178-4

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  • DOI: https://doi.org/10.1007/s00394-020-02178-4

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