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Primary open-angle glaucoma risk prediction with ABCA1 and LOC102723944 variants and their genotype–phenotype correlations in southern Chinese population

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Abstract

Glaucoma is a leading cause of irreversible visual impairment and blindness worldwide. Previous genome-wide association studies have identified caveolin-1 (CAV1), ATP-binding cassette A1 (ABCA1), and forkhead box C1 (FOXC1) loci associated with primary open angle glaucoma (POAG), a major subtype of glaucoma. This study aimed to fine map the association pattern of FOXC1 locus with POAG and determine the correlations of FOXC1, ABCA1, and CAV1 variants with ocular and lipidemic parameters in southern Chinese population. In total, 1291 unrelated Han Chinese subjects were recruited, including 301 high-tension glaucoma (HTG), 126 normal-tension glaucoma (NTG), and 864 control subjects. Twelve variants in FOXC1 locus, and two variants in ABCA1 and CAV1 genes, were genotyped by TaqMan assays. Genetic risk score and genotype–phenotype correlation analyses were conducted. In the FOXC1 locus, LOC102723944 rs6596830, rather than previously reported rs2745572, showed significant association with POAG (P = 8.61 × 10–4, odds ratio (OR) = 0.75) and HTG (P = 3.68 × 10–3, OR = 0.75). ABCA1 rs2487032 was also significantly associated with POAG (P = 3.00 × 10–5, OR = 0.70) and HTG (P = 2.08 × 10–4, OR = 0.70). Joint analysis showed that carriers of homozygous non-protective alleles of ABCA1 rs2487032 and LOC102723944 rs6596830 had 2.99-fold higher risk of POAG (P = 1.27 × 10–3) when compared to those carrying homozygous non-risk alleles. Patients with POAG carrying ABCA1 rs2487032 G allele had higher HDL cholesterol, and those with LOC102723944 rs6596830 A allele had lower LDL. This study revealed individual and joint association of ABCA1 and LOC102723944 variants with POAG in southern Chinese population. Subjects carrying non-protective alleles had increased risk to POAG, and corresponding genotypes would affect the lipid profiles.

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The data can be made available upon reasonable request to the corresponding authors.

References

  • Ahmad H et al (2018) Clinical and functional characterization of a missense ELF2 variant in a CANVAS family. Front Genet 9:85

    Article  PubMed  PubMed Central  Google Scholar 

  • Anderson DR, Chauhan B, Johnson C, Katz J, Patella VM, Drance SM (2000) Criteria for progression of glaucoma in clinical management and in outcome studies. Am J Ophthalmol 130:827–829

    Article  CAS  PubMed  Google Scholar 

  • Bailey JN et al (2016) Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet 48:189–194

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Bonnemaijer PWM et al (2018) Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations. Hum Genet 137:847–862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carreon T, van der Merwe E, Fellman RL, Johnstone M, Bhattacharya SK (2017) Aqueous outflow—a continuum from trabecular meshwork to episcleral veins. Prog Retin Eye Res 57:108–133

    Article  PubMed  Google Scholar 

  • Chen Y et al (2014) Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma. Nat Genet 46:1115–1119

    Article  CAS  PubMed  Google Scholar 

  • Gharahkhani P et al (2014) Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. Nat Genet 46:1120–1125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guan FH et al (2017) The antiproliferative ELF2 isoform, ELF2B, induces apoptosis in vitro and perturbs early lymphocytic development in vivo. J Hematol Oncol 10:75

    Article  PubMed  PubMed Central  Google Scholar 

  • Hysi PG et al (2014) Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nat Genet 46:1126–1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung Y, Han K, Park HYL, Lee SH, Park CK (2020) Metabolic health, obesity, and the risk of developing open-angle glaucoma: metabolically healthy obese patients versus metabolically unhealthy but normal weight patients. Diabetes Metab J 44:414–425

    Article  PubMed  Google Scholar 

  • Kapetanakis VV, Chan MP, Foster PJ, Cook DG, Owen CG, Rudnicka AR (2016) Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. Br J Ophthalmol 100:86–93

    Article  PubMed  Google Scholar 

  • Kim MJ, Kim MJ, Kim HS, Jeoung JW, Park KH (2014) Risk factors for open-angle glaucoma with normal baseline intraocular pressure in a young population: the Korea National Health and Nutrition Examination Survey. Clin Exp Ophthalmol 42:825–832

    Article  PubMed  Google Scholar 

  • Lei Y, Gao Y, Song M, Cao W, Sun X (2020) Retrospective case-control data of serum nitrotyrosine level and clinical biomedical indices in primary glaucoma patients. Data Brief 31:105706

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin YC, Ma C, Hsu WC, Lo HF, Yang VC (2007) Molecular interaction between caveolin-1 and ABCA1 on high-density lipoprotein-mediated cholesterol efflux in aortic endothelial cells. Cardiovasc Res 75:575–583

    Article  CAS  PubMed  Google Scholar 

  • Liu T, Tang C, Shi X (2020) Analysis of variants in Chinese individuals with primary open-angle glaucoma using molecular inversion probe (MIP)-based panel sequencing. Mol vis 26:378–391

    CAS  PubMed  PubMed Central  Google Scholar 

  • MacGregor S et al (2018) Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma. Nat Genet 50:1067–1071

    Article  CAS  PubMed  Google Scholar 

  • Morrison JC, Johnson EC, Cepurna W, Jia L (2005) Understanding mechanisms of pressure-induced optic nerve damage. Prog Retin Eye Res 24:217–240

    Article  PubMed  Google Scholar 

  • Phillips MC (2018) Is ABCA1 a lipid transfer protein? J Lipid Res 59:749–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shon K, Sung KR (2019) Dyslipidemia, dyslipidemia treatment, and open-angle glaucoma in the Korean National Health and Nutrition Examination Survey. J Glaucoma 28:550–556

    Article  PubMed  Google Scholar 

  • Springelkamp H et al (2017) New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics. Hum Mol Genet 26:438–453

    CAS  PubMed  PubMed Central  Google Scholar 

  • Thorleifsson G et al (2010) Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet 42:906–909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang S, Bao X (2019) Hyperlipidemia, blood lipid level, and the risk of glaucoma: a meta-analysis. Investig Ophthalmol Vis Sci 60:1028–1043

    Article  Google Scholar 

  • Wang F, Gu HM, Zhang DW (2014) Caveolin-1 and ATP binding cassette transporter A1 and G1-mediated cholesterol efflux. Cardiovasc Hematol Disord Drug Targets 14:142–148

    Article  CAS  PubMed  Google Scholar 

  • Weinreb RN, Aung T, Medeiros FA (2014) The pathophysiology and treatment of glaucoma: a review. JAMA 311:1901–1911

    Article  PubMed  PubMed Central  Google Scholar 

  • Xue W et al (2020) Caveolin-1 alleviates lipid accumulation in NAFLD associated with promoting autophagy by inhibiting the Akt/mTOR pathway. Eur J Pharmacol 871:172910

    Article  CAS  PubMed  Google Scholar 

  • Yokomichi H et al (2016) Evaluation of the associations between changes in intraocular pressure and metabolic syndrome parameters: a retrospective cohort study in Japan. BMJ Open 6:e010360

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to express our deepest gratitude to all the participants in this study.

Funding

This work was supported by the National Natural Science Foundation of China (82171044 to M.Z.), the Shantou Medical Health, Science and Technology Project Fund (project code: 221116156495101 to T.K.N.), the Special Fund for Science and Technology of Guangdong Province (project code: 2019ST016 to C.H.; 2019ST017 to Z.W.; 2019ST024 to M.Z.), and the internal grant from the Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong (project code: 19-001 to C.P.P.), China, and the General Research Fund from the Research Grants Council (project code: 14105916 to C.P.P.), Hong Kong.

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  1. Zhenggen Wu and Chukai Huang contributed equally to this work.

Authors and Affiliations

  1. Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Guangdong, Shantou, China

    Zhenggen Wu, Chukai Huang, Yuqian Zheng, Xiang-Ling Yuan, Shaowan Chen, Yanxuan Xu, Chi Pui Pang, Mingzhi Zhang & Tsz Kin Ng

  2. Shantou University Medical College, Shantou, Guangdong, China

    Xiang-Ling Yuan & Tsz Kin Ng

  3. Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China

    Li Jia Chen, Chi Pui Pang & Tsz Kin Ng

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  1. Zhenggen Wu
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Contributions

CPP and TKN conception and design. ZW, CH, CPP, MZ and TKN financial support. ZW, CH, and MZ provision of study materials. YZ, SC, and YX collection and/or assembly of data. ZW, XLY and TKN data analysis and interpretation. ZW, XLY and TKN manuscript writing. LJC, CPP and TKN critical revision of manuscript.

Corresponding authors

Correspondence to Chi Pui Pang, Mingzhi Zhang or Tsz Kin Ng.

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Communicated by Shuhua Xu.

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Wu, Z., Huang, C., Zheng, Y. et al. Primary open-angle glaucoma risk prediction with ABCA1 and LOC102723944 variants and their genotype–phenotype correlations in southern Chinese population. Mol Genet Genomics 298, 1343–1352 (2023). https://doi.org/10.1007/s00438-023-02058-6

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