Associations of systemic, serum lipid and lipoprotein metabolic pathway gene variations with polypoidal choroidal vasculopathy in China


Autoři: Ningda Xu aff001;  Hui Xu aff001;  Mingwei Zhao aff001;  Yongsheng Xu aff001;  Lvzhen Huang aff001
Působiště autorů: Department of Ophthalmology, Peking University People’s Hospital Eye Diseases and Optometry Institute, Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center; Beijing, aff001
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226763

Souhrn

Background

To investigate the association of systemic, serum lipids and genetic variants in the high-density lipoprotein (HDL) metabolic pathway with polypoidal choroidal vasculopathy (PCV) in China.

Methods

The case-control study was included 150 controls and 66 cases with PCV. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), HDL, triglycerides (TG), apolipoprotein A1 (APOA1), apolipoprotein B (APOB) together with systemic risk factors including gender, hyperlipidemia, diabetes mellitus (DM), hypertension, coronary artery disease (CAD) and asthma were identified. All subjects were genotyped for four single nucleotide polymorphisms (SNPs) from three genes in the HDL metabolic pathway: rs10468017 of hepatic lipase (LIPC), rs12678919 of lipoprotein lipase (LPL), rs3764261 and rs173539 of cholesterol ester transfer protein (CETP) with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Student’s t-tests, chi-square tests, anova and logistic regression were used to evaluate associations.

Results

Hyperlipidemia was a risk factor (odds ratio (OR) = 1.19, P = 0.001) for PCV. HDL, LDL and APOB levels were associated with PCV (OR = 0.001, P = 0.004; OR = 0.099, P = 0.010; OR = 0.839, P = 0.018). Higher level of TC was potently associated with increased risk of PCV (OR = 109.8, P = 0.000). LIPC rs10468017 was a risk factor for PCV (OR = 11.68, P = 0.000). CETP rs3764261 conferred a decreased risk for PCV (OR = 0.08, P = 0.000). No associations of LPL rs12678919 or CETP rs173539 with PCV were found. Mean level of HDL increased with T allele of the CETP gene (p = 0.026): 1.24 mmol/L (±0.31) for the GG genotype and 1.66 mmol/L (±0.54) for the TT genotype. Additionally, T allele was associated with the following increase in APOA1: 136.78 mg/dl (±20.53) for the CC genotype and 149.57 mg/dl (±22.67) for the TT genotype of LIPC and 137.91 mg/dl (±20.36) for the GG genotype and 162.67 mg/dl (±22.50) for the TT genotype of CETP gene.

Conclusion

Our study suggested that the significant association was found between hyperlipidemia, the serum levels of TC, HDL, LDL and APOB and PCV. The result of present study also showed that the association of LIPC rs10468017 and CETP rs3764261 with PCV.

Klíčová slova:

Asthma – Hyperlipidemia – Hypertension – Cholesterol – Lipids – Medical risk factors – Variant genotypes


Zdroje

1. Byeon S.H., Lee S.C., Oh H.S., Kim S.S., Koh H.J., Kwon O. W. Incidence and clinical patterns of polypoidal choroidal vasculopathy in Korean patients [J]. Japanese Journal of Ophthalmology, 2008; 52(1): 57–62. doi: 10.1007/s10384-007-0498-2 18369702

2. Maruko I, Iida T, Saito M, Nagayama D., Saito K. Clinical Characteristics of Exudative Age-related Macular Degeneration in Japanese Patients [J]. American Journal of Ophthalmology, 2007; 144(1): 0–2200.

3. Liu Y., Wen F., Huang S., Luo G., Yan H., Sun Z., et al. Subtype lesions of neovascular age-related macular degeneration in Chinese patients. Graefes Arch. Clin. Exp. Ophthalmol. 2007; 245: 1441–1445. doi: 10.1007/s00417-007-0575-8 17406882

4. Yuzawa M, Mori R, Kawamura A. The origins of polypoidal choroidal vasculopathy. Br J Ophthalmol, 2005; 89: 602–607. doi: 10.1136/bjo.2004.049296 15834093

5. Rogério A. Costa, Navajas E. V., Farah M. E., Calucci D., Cardillo J. A., Scott I.U. Polypoidal choroidal vasculopathy: angiographic characterization of the network vascular elements and a new treatment paradigm. Prog Retin Eye Res. 2005; 24: 560–586. doi: 10.1016/j.preteyeres.2005.01.001 16005406

6. Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina. 2012; 32 Suppl 1:1–8

7. Koizumi H, Yamagishi T, Yamazaki T, Kinoshita S. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability. Am J Ophthalmol 2013; 155: 305–313. doi: 10.1016/j.ajo.2012.07.018 23022162

8. Spaide RF, Yannuzzi LA, Slakter JS, Sorenson J, Orlach DA. Indocyanine green videoangiography of idiopathic polypoidalchoroidal vasculopathy. Retina. 1995; 15: 100–110. doi: 10.1097/00006982-199515020-00003 7542796

9. Lee J, Zeng J, Hughes G, Chen Y, Grob S, et al. Association of LIPC and advanced age-related macular degeneration. Eye. 2013; 27(2): 265–271. doi: 10.1038/eye.2012.276 23348725

10. Cheung CM, Laude A, Yeo I, Tan SP, Fan Q, et al. Systemic, Ocular and Genetic Risk Factors for Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Singaporeans. Sci Rep. 2017 Jan 25; 7: 41386. doi: 10.1038/srep41386 28120909

11. Neale BM, Fagerness J, Reynolds R, Sobrin L, Parker M, et al. Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proc Natl Acad Sci USA. 2010; 107(16): 7395–400. doi: 10.1073/pnas.0912019107 20385826

12. Tian J, Qin X, Fang K, Chen Q, Hou J, Li J, et al. Association of genetic polymorphisms with response to bevacizumab for neovascular age-related macular degeneration in the Chinese population. Pharmacogenomics. 2012; 13: 779–787. doi: 10.2217/pgs.12.53 22594510

13. Zhang X, Li M, Wen F, Zuo C, Chen H, Wu K, et al. Different impact of high-density lipoprotein related genetic variants on polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population. Exp Eye Res. 2013; 108: 16–22. doi: 10.1016/j.exer.2012.12.005 23274582

14. Iwama D, Tsujikawa A, Sasahara M, Hirami Y, Tamura H, Yoshimura N. Polypoidal choroidal vasculopathy with drusen. Jpn J Ophthalmol. 2008; 52: 116–121. doi: 10.1007/s10384-007-0503-9 18626734

15. Xu Hui, Piao Zhenyu, Ma Xiaoyun, Huang Lvzhen, Zhou Peng, Yu Wenzhen, et al. A functional polymorphism in the promoter of αA-crystallin increases the risk of nAMD. Int J Clin Exp Pathol. 2019; 12(5): 1782–1787.

16. Ueta Takashi, Obata Ryo, Inoue Yuji, Iriyama Aya, Takahashi Hidenori, Yamaguchi Takuhiro, et al. Background Comparison of Typical Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Japanese Patients. Ophthalmology 2009;116:2400–2406. doi: 10.1016/j.ophtha.2009.06.013 19815291

17. Qingyu M, Lvzhen H, Yaoyao S, Yujing Bai, Bin Wang, Wenzhen Yu, et al. Effect of High-Density Lipoprotein Metabolic Pathway Gene Variations and Risk Factors on Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in China [J]. PLOS ONE. 2015; 10(12): e0143924–. doi: 10.1371/journal.pone.0143924 26624898

18. Gotoh N, Kuroiwa S, Kikuchi T. Apolipoprotein E polymorphisms in Japanese patients with polypoidal choroidal vasculopathy and exudative age-related macular degeneration [J]. American Journal of Ophthalmology. 2004; 138(4):0–573.

19. Laude A, Cackett PD, Vithana EN, Yeo IY, Wong D, Koh AH, et al. Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: same or different disease. Prog Retin Eye Res. 2010; 29: 19–29. doi: 10.1016/j.preteyeres.2009.10.001 19854291

20. Kikuchi M, Nakamura M, Ishikawa K, Suzuki T, Nishihara H, Yamakoshi T, et al. Elevated Creactive protein levels in patients with polypoidal choroidal vasculopathy and patients with neovascular age-related macular degeneration. Ophthalmology. 2007; 114: 1722–1727. doi: 10.1016/j.ophtha.2006.12.021 17400294

21. Sun Y., Yu W., Huang L., Hou J., Gong P., Zheng Y., et al. Is asthma related to choroidal neovascularization? PLOS ONE. 2012; 7.

22. Koh AH, Chen LJ, Chen SJ, Chen Y, Giridhar A, Iida T, et al. Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment. Retina (Philadelphia, Pa). 2013; 33(4): 686–716.

23. Chung Y. R., Seo E. J., Kim Y. H., Yang H., & Lee K. Hypertension as a risk factor for recurrent subretinal hemorrhage in polypoidal choroidal vasculopathy [J]. Canadian Journal of Ophthalmology / Journal Canadien d\"Ophtalmologie. 2016; 51(5): 348–353.

24. Kikuchi M, Nakamura M, Ishikawa K, Suzuki T, Nishihara H, Yamakoshi T, et al. Elevated Creactive protein levels in patients with polypoidal choroidal vasculopathy and patients with neovascular age-related macular degeneration. Ophthalmology. 2007; 114: 1722–1727. doi: 10.1016/j.ophtha.2006.12.021 17400294

25. Cho J. H., Ryoo N. K., Cho K. H., Park S. J., Park K.H., Woo S. J. Incidence Rate of Massive Submacular Hemorrhage and its Risk Factors in Polypoidal Choroidal Vasculopathy [J]. American Journal of Ophthalmology. 2016; 169:79–88. doi: 10.1016/j.ajo.2016.06.014 27318076

26. Cody R. Fisher, Deborah A. Ferrington. Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE. Invest Ophthalmol Vis Sci. 2018; 59(4): 41–47.

27. Dashti N. Plasma apolipoproteins and risk for age related maculopathy [J]. British Journal of Ophthalmology. 2006; 90(8):1028–1033.) doi: 10.1136/bjo.2006.093856 16723359

28. Paun CC, Ersoy L, Schick T, Groenewoud JMM, Lechanteur YT, Fauser S, et al. Genetic Variants and Systemic Complement Activation Levels Are Associated With Serum Lipoprotein Levels in Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2015; 56: 7766–7773. doi: 10.1167/iovs.15-17035 26641553

29. Hasham SN, Pillarisetti S. Vascular lipases, inflammation and atherosclerosis. Clin Chim Acta. 2006; 372:179–183. doi: 10.1016/j.cca.2006.04.020 16765928

30. Ming-Zhen Y, Ruo-An H, Chen-Xi Z, You-Xin C. Association of Genes in the High-Density Lipoprotein Metabolic Pathway with Polypoidal Choroidal Vasculopathy in Asian Population: A Systematic Review and Meta-Analysis [J]. Journal of Ophthalmology. 2018; 2018:1–14.

31. Grooth GJ, Klerkx AH, Stroes ES, Stalenhoef AF, Kastelein JJ, Kuivenhoven JA. A review of CETP and its relation to atherosclerosis. J Lipid Res. 2004; 45:1967–74. doi: 10.1194/jlr.R400007-JLR200 15342674

32. Ignacio R Rodr\guez, Larrayoz I M. Cholesterol oxidation in the retina: Implications of 7KCh formation in chronic inflammation and age-related macular degeneration [J]. Journal of Lipid Research. 2010; 51(10): 2847–2862. doi: 10.1194/jlr.R004820 20567027

33. Tserentsoodol N., Gordiyenko N. V., Pascual I., Lee J. W., Rodriguez I. R. Intraretinal lipid transport is dependent on high density lipoprotein-like particles and class B scavenger receptors Molecular Vision. 2006; 12:1319–33. 17110915

34. Nakata I., Yamashiro K., Kawaguchi T., Gotoh N., Nakanishi H., Akagi-Kurashige Y., et al. Association between the cholesteryl ester transfer protein gene and polypoidal choroidal vasculopathy. Investigative Opthalmology and Visual Science, 2013; 54(9): 6068–6073.

35. Liu K., Chen L. J., Lai T. Y. Y., Tam P. O. S., Ho M., Chiang S. W. Y., et al. Genes in the high-density lipoprotein metabolic pathway in age-related macular degeneration and polypoidal choroidal vasculopathy. Ophthalmology. 2014; 121(4): 911–916. doi: 10.1016/j.ophtha.2013.10.042 24393350


Článek vyšel v časopise

PLOS One


2019 Číslo 12