Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Ophthalmology
Published in: BMC Ophthalmology 1/2018

Open Access 01-12-2018 | Research article

Association of Genes implicated in primary angle-closure Glaucoma and the ocular biometric parameters of anterior chamber depth and axial length in a northern Chinese population

Published in: BMC Ophthalmology | Issue 1/2018

Login to get access

Abstract

Background

The membrane frizzled-related protein (MFRP) gene is involved in axial length (AL) regulation and MFRP mutations cause nanophthalmos; also, the hepatocyte growth factor (HGF) gene is reported to result in morphologic changes of the anterior segment and abnormal aqueous regulation that increases the risk of primary angle-closure glaucoma (PACG), while the zinc ring finger 3 (ZNRF3) gene is associated with AL. The present study investigated the association of single nucleotide polymorphisms (SNPs) in ZNRF3, HGF and MFRP with PACG in a northern Chinese population, as well as the association of these SNPs with the ocular biometric parameters of anterior chamber depth (ACD) and AL.

Methods

A total of 500 PACG patients and 720 controls were recruited. All individuals were genotyped for 12 SNPs in three genes (rs7290117, rs2179129, rs4823006 and rs3178915 in ZNRF3; rs5745718, rs12536657, rs12540393, rs17427817 and rs3735520 in HGF, rs2510143, rs36015759 and rs3814762 in MFRP) using an improved multiplex ligation detection reaction (iMLDR) technique. Genotypic distribution was analyzed for Hardy-Weinberg equilibrium. Differences in the allelic and genotypic frequencies were evaluated and adjusted by age and sex. Linkage disequilibrium (LD) patterns were tested and haplotype analysis was conducted by a logistic regression model. Generalized estimation equation (GEE) analysis was conducted using SPSS for primary association testing between genotypes and ocular biometric parameters. Bonferroni corrections for multiple comparisons were performed, and the statistical power was calculated by power and sample size calculations.

Results

The rs7290117 SNP in ZNRF3 was significantly associated with the AL, with a p-value of 0.002. We did not observe any significant associations between the SNPs and PACG or ACD. In a stratification analysis by ethnicity, rs12540393 and rs17427817 in HGF showed a nominal association with PACG in the Hui cohort, although significance was lost after correction.

Conclusions

The present study suggests rs7290117 in ZNRF3 may be involved in the regulation of AL, though our results do not support a contribution of the SNPs we tested in ZNRF3, HGF and MFRP to PACG in northern Chinese people. Further studies in a larger population are warranted to confirm this conclusion.
Literature
1.
Wright C, Tawfik MA, Waisbourd M, Katz LJ. Primary angle-closure glaucoma: an update. Acta Ophthalmol. 2016;94(3):217–25.CrossRef
2.
Sihota R, Ghate D, Mohan S, Gupta V, Pandey RM, Dada T. Ocular parameters in the subgroups of angle closure glaucoma. Eye (Lond). 2008;22(4):521–7.CrossRef
3.
Congdon N, Wang F, Tielsch JM. Issues in the epidemiology and population-based screening of primary angle-closure glaucoma. Surv Ophthalmol. 1992;36(6):411–23.CrossRef
4.
Foster PJ, Baasanhu J, Alsbirk PH, Munkhbayar D, Uranchimeg D, Johnson GJ. Glaucoma in Mongolia. A population-based survey in Hövsgöl province, northern Mongolia. Arch Ophthalmol. 1996;114(10):1235–41.CrossRef
5.
Wang N, Wu H, Fan Z. Primary angle closure glaucoma in Chinese and Western populations. Chin Med J. 2002;115:1706–15.PubMed
6.
Amerasinghe N, Zhang J, Thalamuthu A, He M, Vithana EN, Viswanathan A, et al. The heritability and sibling risk of angle closure in Asians. Ophthalmology. 2011;118(3):480–5.CrossRef
7.
Vithana EN, Khor CC, Qiao C, Nongpiur ME, George R, Chen LJ, et al. Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma. Nat Genet. 2012;44(10):1142–6.CrossRef
8.
Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. Nat Genet. 2016;48(5):556–62.CrossRef
9.
Nongpiur ME, Khor CC, Jia H, Cornes BK, Chen LJ, Qiao C, et al. ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma. PLoS Genet. 2014;10(3):e1004089.CrossRef
10.
Sundin OH, Leppert GS, Silva ED, Yang JM, Dharmaraj S, Maumenee IH, et al. Extreme hyperopia is the result of null mutations in MFRP, which encodes a frizzled-related protein. Proc Natl Acad Sci U S A. 2005;102(27):9553–8.CrossRef
11.
Veerappan S, Pertile KK, Islam AF, Schäche M, Chen CY, Mitchell P, et al. Role of the hepatocyte growth factor gene in refractive error. Ophthalmology. 2010;117(2):239–45.CrossRef
12.
Shen L, Melles RB, Metlapally R, Barcellos L, Schaefer C, Risch N, et al. The Association of Refractive Error with Glaucoma in a multiethnic population. Ophthalmology. 2016;123(1):92–101.CrossRef
13.
Awadalla MS, Thapa SS, Burdon KP, Hewitt AW, Craig JE. The association of hepatocyte growth factor (HGF) gene with primary angle closure glaucoma in the Nepalese population. Mol Vis. 2011;17:2248–54.PubMedPubMedCentral
14.
Jiang Z, Liang K, Ding B, Tan W, Wang J, Lu Y, et al. Hepatocyte growth factor genetic variations and primary angle-closure Glaucoma in the Han Chinese population. PLoS One. 2013;8(4):e60950.CrossRef
15.
Rong SS, Tang FY, Chu WK, Ma L, Yam JC, Tang SM, et al. Genetic associations of primary angle-closure disease: a systematic review and meta-analysis. Ophthalmology. 2016;123(6):1211–21.CrossRef
16.
Cheng CY, Schache M, Ikram MK, Young TL, Guggenheim JA, Vitart V, et al. Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. Am J Hum Genet. 2013;93(2):264–77.CrossRef
17.
Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86:238–42.CrossRef
18.
Awadalla MS, Burdon KP, Thapa SS, Hewitt AW. Craig JE. A cross-ethnicity investigation of genes previously implicated in primary angle closure glaucoma. Mol Vis. 2012;18:2247–54.PubMedPubMedCentral
19.
Shi H, Zhu R, Hu N, Shi J, Zhang J, Jiang L, et al. Association of frizzled-related protein (MFRP) and heat shock protein 70 (HSP70) single nucleotide polymorphisms with primary angle closure in a Han Chinese population: Jiangsu eye study. Mol Vis. 2013;19:128–34.PubMedPubMedCentral
20.
Shi H, Zhang J, Zhu R, Hu N, Lu H, Yang M, et al. Primary angle closure and sequence variants within MicroRNA binding sites of genes involved in eye development. PLoS One. 2016;11(11):e0166055.CrossRef
21.
Zeger SL, Liang K-Y, Albert PS. Models for longitudinal data: a generalized estimating equation approach. Biometrics. 1988;44:1049–60.CrossRef
22.
Hanley JA, Negassa A, MDd E, Forrester JE. Statistical analysis of correlated data using generalized estimating equations: an orientation. Am J Epidemiol. 2003;157(4):364–75.CrossRef
23.
Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012;485(7397):195–200.CrossRef
24.
Fuhrmann S. Wnt signaling in eye organogenesis. Organ. 2008;4(2):60–7.
25.
Li Q, Weng J, Mohan RR, Bennett GL, Schwall R, Wang ZF, et al. Hepatocyte growth factor and hepatocyte growth factor receptor in the lacrimal gland, tears, and Cornea. Invest Ophthalmol Vis Sci. 1996;37(5):727–39.PubMed
26.
He PM, He S, Garner JA, Ryan SJ, Hinton DR. Retinal pigment epithelial cells secrete and respond to hepatocyte growth factor. Biochem Biophys Res Commun. 1998;249(1):253–7.CrossRef
27.
Wordinger RJ, Clark AF, Agarwal R, Lambert W, McNatt L, Wilson SE, et al. Cultured human trabecular meshwork cells express functional growth factor receptors. Invest Ophthalmol Vis Sci. 1998;39(9):1575–89.PubMed
28.
Katoh M. Molecular cloning and characterization of MFRP, a novel gene encoding a membrane-type frizzled-related protein. Biochem Biophys Res Commun. 2001;282(1):116–23.CrossRef
29.
Wang IJ, Lin S, Chiang TH, Chen ZT, Lin LL, Hung PT, et al. The association of membrane frizzled-related protein (MFRP) gene with acute angle-closure glaucoma – a pilot study. Mol Vis. 2008;14:1673–9.PubMedPubMedCentral
Metadata
Title
Association of Genes implicated in primary angle-closure Glaucoma and the ocular biometric parameters of anterior chamber depth and axial length in a northern Chinese population
Publication date
01-12-2018
Published in
BMC Ophthalmology / Issue 1/2018
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-018-0934-8

Other articles of this Issue 1/2018

BMC Ophthalmology 1/2018 Go to the issue

Case report

A rare case of scleral buckle infection with Curvularia species

Research article

Mitochondria-targeted antioxidant SKQ1 protects cornea from oxidative damage induced by ultraviolet irradiation and mechanical injury

Research article

A qualitative study on gender barriers to eye care access in Cambodia

Research article

The effect of ranibizumab and aflibercept treatment on the prevalence of outer retinal tubulation and its influence on retreatment in neovascular age-related macular degeneration

Case report

Giant cell arteritis presenting as bilateral anterior ischemic optic neuropathy: a biopsy-proven case report in Chinese patient

Research article

Prevalence and causes of blindness, visual impairment among different ethnical minority groups in Xinjiang Uygur autonomous region, China