Association of HK2 and NCK2 with normal-tension glaucoma in a population from the Republic of Korea

  • Seung-Hyun Jung
  • Young Chun Lee
  • Mee Yon Lee
  • Hye-Young ShinEmail author



Previous studies have reported the association of HK2 and NCK2 genes with normal-tension glaucoma (NTG) in Japan, but there has been no follow-up study in other countries, so the relevance of these genes to NTG appears uncertain at present. Thus, we investigated the relationship between the HK2 and NCK2 genes and NTG in a Korean NTG cohort.


In total, 154 unrelated Korean patients with NTG and 101 normal Korean controls were recruited. Thus, a total of 255 participants were analyzed for NCK2 (rs2033008) and HK2 (rs678350) gene polymorphisms.


The minor allele frequency (MAF) of rs678350 was significantly higher in NTG patients (MAF = 0.32) than in controls (MAF = 0.23) (OR, 1.586; 95% CI, 1.058 to 2.375; P = 0.028). This trend was more significant in the dominant model (OR, 1.908; 95% CI, 1.144 to 3.180; P = 0.015). When we performed logistic regression analysis to adjust for age, both the allelic and dominant models were still statistically significant. No significant difference was observed in rs2033008 allele or genotype frequencies between the NTG patients and control subjects.


The current study suggested that HK2 gene polymorphism may contribute to the genetic susceptibility to NTG.


Genotyping Hexokinase 2 Non-catalytic region of tyrosine kinase adaptor protein 2 Normal-tension glaucoma Single nucleotide polymorphism South Korea 


Author contributions

Conceptualization: Seung-Hyun Jung, Mee Yon Lee, Hye-Young Shin

Data collection: Young Chun Lee, Mee Yon Lee, Hye-Young Shin

Formal analysis: Seung-Hyun Jung, Hye-Young Shin

Methodology: Seung-Hyun Jung, Hye-Young Shin

Interpretation of the data: Seung-Hyun Jung, Hye-Young Shin

Funding acquisition: Young Chun Lee, Hye-Young Shin

Supervision and validation: Young Chun Lee, Seung-Hyun Jung, Hye-Young Shin

Writing—original draft: Seung-Hyun Jung, Hye-Young Shin

Writing—review and editing: Seung-Hyun Jung, Young Chun Lee, Mee Yon Lee, Hye-Young Shin


This study was funded by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. NRF-2018R1D1A1B07047231), the 2018 Cheil-Nammyung Foundation Research Funds, and the Catholic University of Korea Uijeongbu St. Mary’s Hospital Clinical Research Laboratory Foundation made in the program year of 2019 (UJBCRL201823).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of the Uijeongbu St. Mary’s Hospital of Korea and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

417_2019_4467_MOESM1_ESM.docx (27 kb)
ESM 1 (DOCX 27 kb)


  1. 1.
    Janssen SF, Gorgels TG, Ramdas WD, Klaver CC, van Duijn CM, Jansonius NM, Bergen AA (2013) The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog Retin Eye Res 37:31–67. CrossRefGoogle Scholar
  2. 2.
    Kim CS, Seong GJ, Lee NH, Song KC, Namil Study Group KGS (2011) Prevalence of primary open-angle glaucoma in Central South Korea the Namil study. Ophthalmology 118:1024–1030. CrossRefGoogle Scholar
  3. 3.
    Wang YX, Xu L, Yang H, Jonas JB (2010) Prevalence of glaucoma in North China: the Beijing Eye Study. Am J Ophthalmol 150:917–924. CrossRefGoogle Scholar
  4. 4.
    Foster PJ, Baasanhu J, Alsbirk PH, Munkhbayar D, Uranchimeg D, Johnson GJ (1996) Glaucoma in Mongolia. A population-based survey in Hovsgol province, northern Mongolia. Arch Ophthalmol 114:1235–1241. CrossRefGoogle Scholar
  5. 5.
    Iwase A, Suzuki Y, Araie M, Yamamoto T, Abe H, Shirato S, Kuwayama Y, Mishima HK, Shimizu H, Tomita G, Inoue Y, Kitazawa Y, Tajimi Study Group JGS (2004) The prevalence of primary open-angle glaucoma in Japanese: the Tajimi study. Ophthalmology 111:1641–1648. Google Scholar
  6. 6.
    Stoilova D, Child A, Trifan OC, Crick RP, Coakes RL, Sarfarazi M (1996) Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region. Genomics 36:142–150. CrossRefGoogle Scholar
  7. 7.
    Charlesworth JC, Stankovich JM, Mackey DA, Craig JE, Haybittel M, Westmore RN, Sale MM (2006) Confirmation of the adult-onset primary open angle glaucoma locus GLC1B at 2cen-q13 in an Australian family. Ophthalmologica 220:23–30. CrossRefGoogle Scholar
  8. 8.
    Akiyama M, Yatsu K, Ota M, Katsuyama Y, Kashiwagi K, Mabuchi F, Iijima H, Kawase K, Yamamoto T, Nakamura M, Negi A, Sagara T, Kumagai N, Nishida T, Inatani M, Tanihara H, Ohno S, Inoko H, Mizuki N (2008) Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for NTG. Br J Ophthalmol 92:1293–1296. CrossRefGoogle Scholar
  9. 9.
    Shi D, Funayama T, Mashima Y, Takano Y, Shimizu A, Yamamoto K, Mengkegale M, Miyazawa A, Yasuda N, Fukuchi T, Abe H, Ideta H, Nishida K, Nakazawa T, Richards JE, Fuse N (2013) Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population. PLoS One 8:e54115. CrossRefGoogle Scholar
  10. 10.
    Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575. CrossRefGoogle Scholar
  11. 11.
    Kontis V, Bennett JE, Mathers CD, Li G, Foreman K, Ezzati M (2017) Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet 389:1323–1335. CrossRefGoogle Scholar
  12. 12.
    Kim M, Kim TW, Park KH, Kim JM (2012) Risk factors for primary open-angle glaucoma in South Korea: the Namil study. Jpn J Ophthalmol 56:324–329. CrossRefGoogle Scholar
  13. 13.
    Suzuki Y, Iwase A, Araie M, Yamamoto T, Abe H, Shirato S, Kuwayama Y, Mishima HK, Shimizu H, Tomita G, Inoue Y, Kitazawa Y, Tajimi Study G (2006) Risk factors for open-angle glaucoma in a Japanese population: the Tajimi study. Ophthalmology 113:1613–1617. CrossRefGoogle Scholar
  14. 14.
    Ahn KJ, Kim J, Yun M, Park JH, Lee JD (2009) Enzymatic properties of the N- and C-terminal halves of human hexokinase II. BMB Rep 42:350–355CrossRefGoogle Scholar
  15. 15.
    da-Silva WS, Gomez-Puyou A, de Gomez-Puyou MT, Moreno-Sanchez R, De Felice FG, de Meis L, Oliveira MF, Galina A (2004) Mitochondrial bound hexokinase activity as a preventive antioxidant defense: steady-state ADP formation as a regulatory mechanism of membrane potential and reactive oxygen species generation in mitochondria. J Biol Chem 279:39846–39855. CrossRefGoogle Scholar
  16. 16.
    Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen JE, Gottlob K, Chandel NS, Thompson CB, Robey RB, Hay N (2004) Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell 16:819–830. CrossRefGoogle Scholar
  17. 17.
    Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S (2002) Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor. Biochem Biophys Res Commun 294:1087–1092. CrossRefGoogle Scholar
  18. 18.
    Round JE, Sun H (2011) The adaptor protein Nck2 mediates Slit1-induced changes in cortical neuron morphology. Mol Cell Neurosci 47:265–273. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Cancer Evolution Research Center, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
  2. 2.Department of Ophthalmology, Uijeongbu St. Mary’s Hospital, College of MedicineThe Catholic University of KoreaUijeongbu-siRepublic of Korea

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