Skip to main content
SpringerLink
Log in

Genetic association study between INSULIN pathway related genes and high myopia in a Han Chinese population

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

To investigate the association between insulin (INS) pathway related genes, including INS, insulin receptor (INSR), insulin receptor substrate 1 (IRS1), insulin-like growth factor 2 (IGF2), IGF2 receptor (IGF2R) and IGF binding protein 1 (IGFBP1), and high myopia (HM) in a Han Chinese population, we have genotyped 24 single nucleotide polymorphisms (SNPs) of these genes in this cohort by Sequenom MassARRAY method. The genotyping data was analyzed by χ2 test and the linkage disequilibrium block structure was examined by Haploview software. SNPs in the INS-IGF2 region (rs2070762 and rs1003483), and the INSR gene (rs3745551 and rs2229429) showed significant association with HM (allelic P = 0.0085, 0.0494, 0.0171 and 0.0238, respectively). Under the model of risk genotype combination of INSR and IRS1, carrying the variant allele (A) of the IRS1 Gly972Arg SNP (rs1801278) further increased the risk among the rs2229429T allele carriers (odds ratio 6.865, 95 % confidence interval 1.533–30.745). None of the SNPs in the IGF2R and IGFBP1 genes were found to be significantly associated with HM. Genetic variants in the insulin signaling pathway genes may increase the susceptibility of high myopia in Han Chinese.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. He M, Zeng J, Liu Y, Xu J, Pokharel GP, Ellwein LB (2004) Refractive error and visual impairment in urban children in Southern China. Invest Ophthalmol Vis Sci 45(3):793–799

    Article  PubMed  Google Scholar 

  2. Pan CW, Ramamurthy D, Saw SM (2012) Worldwide prevalence and risk factors for myopia. Ophthalmic Physiol Opt 32(1):3–16

    Article  PubMed  Google Scholar 

  3. He M, Zheng Y, Xiang F (2009) Prevalence of myopia in urban and rural children in mainland China. Optom Vis Sci 86(1):40–44

    Article  PubMed  Google Scholar 

  4. Morgan I, Rose K (2005) How genetic is school myopia? Prog Retin Eye Res 24(1):1–38

    Article  PubMed  Google Scholar 

  5. Sawada A, Tomidokoro A, Araie M, Iwase A, Yamamoto T (2008) Refractive errors in an elderly Japanese population: the Tajimi study. Ophthalmology 115(2):363–370

    Article  PubMed  Google Scholar 

  6. Wong TY, Foster PJ, Hee J, Ng TP, Tielsch JM, Chew SJ, Johnson GJ, Seah SK (2000) Prevalence and risk factors for refractive errors in adult Chinese in Singapore. Invest Ophthalmol Vis Sci 41(9):2486–2494

    CAS  PubMed  Google Scholar 

  7. Vitale S, Sperduto RD, Ferris FL 3rd (2009) Increased prevalence of myopia in the United States between 1971–1972 and 1999–2004. Arch Ophthalmol 127(12):1632–1639

    Article  PubMed  Google Scholar 

  8. Kempen JH, Mitchell P, Lee KE, Tielsch JM, Broman AT, Taylor HR, Ikram MK, Congdon NG, O’Colmain BJ (2004) The prevalence of refractive errors among adults in the United States, Western Europe, and Australia. Arch Ophthalmol 122(4):495–505

    Article  PubMed  Google Scholar 

  9. Resnikoff S, Pascolini D, Mariotti SP, Pokharel GP (2008) Global magnitude of visual impairment caused by uncorrected refractive errors in 2004. Bull World Health Organ 86(1):63–70

    Article  PubMed Central  PubMed  Google Scholar 

  10. Banker AS, Freeman WR (2001) Retinal detachment. Ophthalmol Clin North Am 14(4):695–704

    Article  CAS  PubMed  Google Scholar 

  11. Saw SM, Gazzard G, Shih-Yen EC, Chua WH (2005) Myopia and associated pathological complications. Ophthalmic Physiol Opt 25(5):381–391

    Article  PubMed  Google Scholar 

  12. Katz J, Tielsch JM, Sommer A (1997) Prevalence and risk factors for refractive errors in an adult inner city population. Invest Ophthalmol Vis Sci 38(2):334–340

    CAS  PubMed  Google Scholar 

  13. Saw SM, Chua WH, Hong CY, Wu HM, Chan WY, Chia KS, Stone RA, Tan D (2002) Nearwork in early-onset myopia. Invest Ophthalmol Vis Sci 43(2):332–339

    PubMed  Google Scholar 

  14. Ip JM, Saw SM, Rose KA, Morgan IG, Kifley A, Wang JJ, Mitchell P (2008) Role of near work in myopia: findings in a sample of Australian school children. Invest Ophthalmol Vis Sci 49(7):2903–2910

    Article  PubMed  Google Scholar 

  15. Rose KA, Morgan IG, Ip J, Kifley A, Huynh S, Smith W, Mitchell P (2008) Outdoor activity reduces the prevalence of myopia in children. Ophthalmology 115(8):1279–1285

    Article  PubMed  Google Scholar 

  16. Saw SM, Hong CY, Chia KS, Stone RA, Tan D (2001) Nearwork and myopia in young children. Lancet 357(9253):390

    Article  CAS  PubMed  Google Scholar 

  17. Young TL, Metlapally R, Shay AE (2007) Complex trait genetics of refractive error. Arch Ophthalmol 125(1):38–48

    Article  CAS  PubMed  Google Scholar 

  18. Morgan IG, Ohno-Matsui K, Saw SM (2012) Myopia. Lancet 379(9827):1739–1748

    Article  PubMed  Google Scholar 

  19. Ma JH, Shen SH, Zhang GW, Zhao DS, Xu C, Pan CM, Jiang H, Wang ZQ, Song HD (2010) Identification of a locus for autosomal dominant high myopia on chromosome 5p13.3–p15.1 in a Chinese family. Mol Vis 16:2043–2054

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Shi Y, Qu J, Zhang D, Zhao P, Zhang Q, Tam PO, Sun L, Zuo X, Zhou X, Xiao X, Hu J, Li Y, Cai L, Liu X, Lu F, Liao S, Chen B, He F, Gong B, Lin H, Ma S, Cheng J, Zhang J, Chen Y, Zhao F, Yang X, Yang C, Lam DS, Li X, Shi F, Wu Z, Lin Y, Yang J, Li S, Ren Y, Xue A, Fan Y, Li D, Pang CP, Zhang X, Yang Z (2011) Genetic variants at 13q12.12 are associated with high myopia in the Han Chinese population. Am J Hum Genet 88(6):805–813

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Shi Y, Li Y, Zhang D, Zhang H, Lu F, Liu X, He F, Gong B, Cai L, Li R, Liao S, Ma S, Lin H, Cheng J, Zheng H, Shan Y, Chen B, Hu J, Jin X, Zhao P, Chen Y, Zhang Y, Lin Y, Li X, Fan Y, Yang H, Wang J, Yang Z (2011) Exome sequencing identifies ZNF644 mutations in high myopia. PLoS Genet 7(6):e1002084

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Baird PN, Schache M, Dirani M (2010) The Genes in Myopia (GEM) study in understanding the aetiology of refractive errors. Prog Retin Eye Res 29(6):520–542. doi:10.1016/j.preteyeres.2010.05.004

    Article  PubMed  Google Scholar 

  23. Young TL (2009) Molecular genetics of human myopia: an update. Optom Vis Sci 86(1):E8–E22

    Article  PubMed Central  PubMed  Google Scholar 

  24. Feldkaemper MP, Neacsu I, Schaeffel F (2009) Insulin acts as a powerful stimulator of axial myopia in chicks. Invest Ophthalmol Vis Sci 50(1):13–23

    Article  PubMed  Google Scholar 

  25. Gosbell AD, Favilla I, Baxter KM, Jablonski P (2000) Insulin receptor and insulin receptor substrate-I in rat retinae. Clin Exp Ophthalmol 28(3):212–215

    Article  CAS  Google Scholar 

  26. Metlapally R, Ki CS, Li YJ, Tran-Viet KN, Abbott D, Malecaze F, Calvas P, Mackey DA, Rosenberg T, Paget S, Guggenheim JA, Young TL (2010) Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort. Invest Ophthalmol Vis Sci 51(9):4476–4479

    Article  PubMed Central  PubMed  Google Scholar 

  27. Rydzanicz M, Nowak DM, Karolak JA, Frajdenberg A, Podfigurna-Musielak M, Mrugacz M, Gajecka M (2011) IGF-1 gene polymorphisms in Polish families with high-grade myopia. Mol Vis 17:2428–2439

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Mak JY, Yap MK, Fung WY, Ng PW, Yip SP (2012) Association of IGF1 gene haplotypes with high myopia in Chinese adults. Arch Ophthalmol 130(2):209–216

    Article  CAS  PubMed  Google Scholar 

  29. Zhuang W, Yang P, Li Z, Sheng X, Zhao J, Li S, Yang X, Xiang W, Rong W, Liu Y, Zhang F (2012) Association of insulin-like growth factor-1 polymorphisms with high myopia in the Chinese population. Mol Vis 18:634–644

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Tang RH, Tan J, Deng ZH, Zhao SZ, Miao YB, Zhang WJ (2012) Insulin-like growth factor-2 antisense oligonucleotides inhibits myopia by expression blocking of retinal insulin-like growth factor-2 in guinea pig. Clin Exp Ophthalmol 40(5):503–511

    Article  Google Scholar 

  31. Deng ZH, Tan J, Liu SZ, Zhao SZ, Wang JT (2010) The correlation between the regulation of recombinant human IGF-2 on eye growth and form-deprivation in guinea pig. Graefes Arch Clin Exp Ophthalmol 248(4):519–525

    Article  PubMed  Google Scholar 

  32. Smith AV (2008) Manipulating HapMap Data Using HaploView. CSH Protoc 2008:pdb prot5025

  33. Wagner K, Hemminki K, Grzybowska E, Klaes R, Butkiewicz D, Pamula J, Pekala W, Zientek H, Mielzynska D, Siwinska E, Forsti A (2004) The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer. Carcinogenesis 25(12):2473–2478

    Article  CAS  PubMed  Google Scholar 

  34. Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH (2001) Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 69(1):138–147

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Pechlivanis S, Pardini B, Bermejo JL, Wagner K, Naccarati A, Vodickova L, Novotny J, Hemminki K, Vodicka P, Forsti A (2007) Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect. Endocr Relat Cancer 14(3):733–740

    Article  CAS  PubMed  Google Scholar 

  36. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265

    Article  CAS  PubMed  Google Scholar 

  37. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296(5576):2225–2229

    Article  CAS  PubMed  Google Scholar 

  38. Kusakari T, Sato T, Tokoro T (2001) Visual deprivation stimulates the exchange of the fibrous sclera into the cartilaginous sclera in chicks. Exp Eye Res 73(4):533–546

    Article  CAS  PubMed  Google Scholar 

  39. Penha AM, Schaeffel F, Feldkaemper M (2011) Insulin, insulin-like growth factor-1, insulin receptor, and insulin-like growth factor-1 receptor expression in the chick eye and their regulation with imposed myopic or hyperopic defocus. Mol Vis 17:1436–1448

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Malodobra M, Pilecka A, Gworys B, Adamiec R (2011) Single nucleotide polymorphisms within functional regions of genes implicated in insulin action and association with the insulin resistant phenotype. Mol Cell Biochem 349(1–2):187–193

    Article  CAS  PubMed  Google Scholar 

  41. Sachdev D, Yee D (2007) Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther 6(1):1–12

    Article  CAS  PubMed  Google Scholar 

  42. Pavelic K, Bukovic D, Pavelic J (2002) The role of insulin-like growth factor 2 and its receptors in human tumors. Mol Med 8(12):771–780

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Killian JK, Oka Y, Jang HS, Fu X, Waterland RA, Sohda T, Sakaguchi S, Jirtle RL (2001) Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations. Hum Mutat 18(1):25–31

    Article  CAS  PubMed  Google Scholar 

  44. Almind K, Inoue G, Pedersen O, Kahn CR (1996) A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies. J Clin Invest 97(11):2569–2575

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Kadowaki T, Kadowaki H, Rechler MM, Serrano-Rios M, Roth J, Gorden P, Taylor SI (1990) Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance. J Clin Invest 86(1):254–264

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the patients and their families for their participation. This work was supported by grants from the National Basic Research Program of China (973 Program, 2011CB504604 to ZY); the Natural Science Foundation of China (81271047 to XL; 81170882 to YS; 81170883 to ZY; 81100693 to CQ; 81070761 and 81241001 to FL); the Department of Science and Technology of Sichuan Province (2012JQ0023 to YS); the Department of Sichuan Provincial Health (120121 to XL).

Conflict of Interest

All authors have declared that they have no conflict of interest.

Author information

Authors and Affiliations

  1. School of materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China

    Xiaoqi Liu, Pu Wang, Zhenglin Yang & Yi Shi

  2. The Sichuan Key Laboratory for Human Disease Gene Study, Clinical Laboratory Department, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, Sichuan, China

    Xiaoqi Liu, Pu Wang, Hong Zheng, Bo Gong, Shi Ma, He Lin, Jing Cheng, Zhenglin Yang, Fang Lu & Yi Shi

  3. Department of Ophthalmology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, Sichuan, China

    Chao Qu

  4. School of Clinical Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, China

    Xiaoqi Liu, Zhenglin Yang, Fang Lu & Yi Shi

  5. Center for Human Molecular Biology & Genetics, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, 32 The First Ring Road West 2, Chengdu, 610072, Sichuan, China

    Fang Lu & Yi Shi

Authors
  1. Xiaoqi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shi Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. He Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jing Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhenglin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fang Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yi Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi Shi.

Additional information

Xiaoqi Liu, Pu Wang, Chao Qu and Hong Zheng have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Wang, P., Qu, C. et al. Genetic association study between INSULIN pathway related genes and high myopia in a Han Chinese population. Mol Biol Rep 42, 303–310 (2015). https://doi.org/10.1007/s11033-014-3773-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3773-6

Keywords

Search

Navigation