ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.
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ABSTRACT:
SUBMITTER: Nongpiur ME
PROVIDER: S-EPMC3945113 | biostudies-literature | 2014 Mar
REPOSITORIES: biostudies-literature
Publications
ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.
Nongpiur Monisha E ME Khor Chiea Chuen CC Jia Hongyan H Cornes Belinda K BK Chen Li-Jia LJ Qiao Chunyan C Nair K Saidas KS Cheng Ching-Yu CY Xu Liang L George Ronnie R Tan Do D Abu-Amero Khaled K Perera Shamira A SA Ozaki Mineo M Mizoguchi Takanori T Kurimoto Yasuo Y Low Sancy S Tajudin Liza-Sharmini A LS Ho Ching-Lin CL Tham Clement C Y CC Soto Ileana I Chew Paul T K PT Wong Hon-Tym HT Shantha Balekudaru B Kuroda Masako M Osman Essam A EA Tang Guangxian G Fan Sujie S Meng Hailin H Wang Hua H Feng Bo B Yong Victor H K VH Ting Serena M L SM Li Yang Y Wang Ya-Xing YX Li Zheng Z Lavanya Raghavan R Wu Ren-Yi RY Zheng Ying-Feng YF Su Daniel H DH Loon Seng-Chee SC Yong Vernon K Y VK Allingham R Rand RR Hauser Michael A MA Soumittra Nagaswamy N Ramprasad Vedam L VL Waseem Naushin N Yaakub Azhany A Chia Kee-Seng KS Kumaramanickavel Govindasamy G Wong Tina T TT How Alicia C AC Chau Tran Nguyen Bich TN Simmons Cameron P CP Bei Jin-Xin JX Zeng Yi-Xin YX Bhattacharya Shomi S SS Zhang Mingzhi M Tan Donald T DT Teo Yik-Ying YY Al-Obeidan Saleh A SA Hon Do Nhu DN Tai E-Shyong ES Saw Seang-Mei SM Foster Paul J PJ Vijaya Lingam L Jonas Jost B JB Wong Tien-Yin TY John Simon W M SW Pang Chi-Pui CP Vithana Eranga N EN Wang Ningli N Aung Tin T
PLoS genetics 20140306 3
Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-contro ...[more]
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Project description: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.
| S-EPMC6198425 | biostudies-literature
Project description:PurposeTo investigate the biometric differences of anterior segment parameters between fellow eyes of acute primary angle closure (F-APAC) and chronic primary angle closure glaucoma (F-CPACG) to get information about differences between APAC and CPAC.MethodsPatients with F-APAC and F-CPACG without prior treatment were enrolled from glaucoma clinics. Parameters were measured on ultrasound biomicroscopy images, including pupil diameter, lens vault (LV), anterior chamber depth, anterior chamber width, iris area, iris thickness (IT 750 and 2000), angle-opening distance (AOD 500 and 750), trabecular-iris space area (TISA 500 and 750), trabecular iris angle (TIA 500 and 750), trabecular-ciliary angle, and ciliary process area. Multivariate logistic regression analysis was performed to determine the most important parameters associated with F-APAC compared with F-CPACG.ResultsFifty-five patients with APAC and 55 patients with CPACG were examined. The anterior chamber depth, IT 750, AOD 750, trabecular iris angle 750, and trabecular-ciliary angle were smaller, and LV and ciliary process area were greater in F-APAC as compared with F-CPACG (P ≤ 0.01). Multivariate logistic regression showed that thinner IT 750, smaller AOD 750, and larger LV were significantly associated with F-APAC (P < 0.01). IT 750 (area under the curve, 0.703) performed relatively better than AOD 750 (area under the curve, 0.696) in distinguishing F-APAC from F-CPACG, with the best cutoff of 0.404 mm and 0.126 mm, respectively.ConclusionsCompared with F-CPACG, F-APAC had thinner peripheral iris, narrower anterior chamber angle, shallower anterior chamber depth, greater LV, larger and anteriorly positioned ciliary body. IT 750, AOD 750, and LV played important roles in distinguishing eyes predisposed to APAC or CPAC.
| S-EPMC8572512 | biostudies-literature
Project description:AimTo estimate the risk of blindness with primary angle-closure glaucoma (PACG) compared to primary open-angle glaucoma (POAG) in those population-based studies that reported blindness rates for both PACG and POAG.MethodA systematic search was performed in PubMed for articles published in English between 2000 and 2020 reporting the prevalence of POAG as well as PACG among various ethnic populations. A study was included if it was (1) population-based (2) had published prevalence and blindness rates for both PACG and POAG in the same cohort. (3) Glaucoma was defined as per the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) criteria. The proportion of blindness for both POAG and PACG for each study and the cumulative proportion taking all the studies were calculated.ResultsWe included 23 studies with 78,434 participants. POAG was diagnosed in 1702 persons with 151 (8.9%) blind. There were 724 cases of PACG with 196 (27.0%) blind. The risk ratio of blindness in PACG to POAG varied from 0.73 to 10.6 among the studies. The cumulative risk ratio was 2.39 (95% confidence interval (CI); 1.99, 2.87). Risk ratios for studies including visual field restriction while defining blindness were similar to studies that did not (1.92 vs 2.64, P = 0.11). Risk ratios were also similar for studies that used greater than 2 instead of 3 or more quadrants of iridotrabecular contact to define angle closure (2.79 vs 2.25).ConclusionPrimary angle-closure disease is more likely to be associated with blindness.
| S-EPMC9582001 | biostudies-literature
Project description:To investigate the association of peripheral anterior synechiae (PAS) with intraocular pressure (IOP) and anterior-segment parameters in subjects with primary angle-closure glaucoma (PACG). A total of 267 subjects with PACG were recruited and underwent gonioscopy and anterior-segment optical coherence tomography (ASOCT). Customized software was used to measure ASOCT parameters, including angle opening distance (AOD750) and trabecular-iris-space-area (TISA750) at 750 µm from the scleral spur, anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness (IT750), iris area (IAREA), and lens vault (LV). Presenting IOP was defined as the first IOP reading before the initiation of IOP-lowering treatment. The mean age of the 267 subjects was 67.0 ± 8.9 years, 140 (52.4%) were male, and 246 (92.1%) were of Chinese ethnicity. PAS was present in 122 (45.7%) subjects, and was most frequently found in the superior quadrant (79.5%). Subjects with PAS had greater presenting IOP (28.7 ± 12.9 vs 22.4 ± 9.7 mmHg, p < 0.001), narrower AOD750 (p < 0.001), smaller TISA750 (p < 0.001), ACD (p = 0.04), ACA (p = 0.02), ACV (p = 0.01) and larger LV (p = 0.01) compared to PACG eyes without PAS. No significant differences were noted for iris parameters. A multivariate logistic regression analysis showed that higher presenting IOP (β = 0.20, p < 0.001), worse visual field mean deviation (β = - 0.20, p = 0.01) and narrower AOD750 (β = - 0.25, p = 0.03) were the only parameters that significantly correlated with the extent of PAS in clock hours. Almost one-half of the subjects with PACG demonstrated PAS; these eyes were associated with higher presenting IOP, smaller anterior segment dimensions and more severe disease.
| S-EPMC8260708 | biostudies-literature
Project description:Introduction PLEKHA7, ABCC5, and KALRN have been identified as susceptible genetic markers related to glaucoma. We aimed to investigate the association between the identified susceptible genetic markers PLEKHA7 rs11024102, ABCC5 rs17217796, and KALRN rs1392912 in the progression of primary angle-closure glaucoma (PACG) in Malay patients. Methods For this study, 163 Malay patients with PACG were recruited from April 2015 to April 2017 at Hospital Universiti Sains Malaysia and Hospital Raja Perempuan Zainab II, Kota Bharu. Venesection was performed. DNA was extracted using a commercial DNA extraction kit. The primer was optimized for rs11024102, rs17217796, and rs1392912 of the PLEKHA7, ABCC5, and KALRN genes, respectively. Polymerase chain reaction (PCR) was performed, and PCR products were purified. A DNA sequencer was used to identify polymorphisms. Progression was based on the agreement between the Advanced Glaucoma Intervention Study scoring system and the Hodapp-Parrish and Anderson staging system. The scoring was conducted on two reliable consecutive Humphrey visual fields (HVFs) during the recruitment period and two baseline HVFs obtained when the diagnosis was made. Based on the scoring, patients were grouped into progressed and non-progressed. A chi-square test was used to analyze the association between the genetic markers and the progression of PACG. Results One hundred and sixty-three Malay patients with PACG (58 men and 105 women) were recruited. Twenty-nine patients (18%) had visual field progression of PACG after a mean (SD) follow-up of 6.0 (1.0) years. The minor allele frequencies for PLEKHA7 rs11024102 (G/A), ABCC5 rs17217796 (C/G), and KALRN rs1392912 (A/G) were 0.44, 0.08, and 0.48, respectively. We found that rs11024102 (p=0.828), rs17217796 (p=0.865), and rs1392912 (p=0.684) were not associated with PACG progression in the Malay patients. Conclusion Although PLEKHA7 and ABCC5 were found to be genetic markers associated with the risk of PACG, they played no roles in PACG progression in the Malay population. Moreover, KALRN was not significantly associated with PACG progression. Other susceptible genetic markers may be responsible for PACG progression.
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Project description:Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07) or with PAC/PACG subgroups (Pc > 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P < 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, Pc = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P > 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG.
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Project description:Primary Angle Closure Glaucoma (PACG) is one of the most common types of glaucoma affecting over 15 million individuals worldwide. Family history and ethnicity are strongly associated with the development of the disease, suggesting that one or more genetic factors contribute to PACG. Although strictly heritable disease-causing mutations have not been identified, a number of recent association studies have pointed out genetic factors that appear to contribute to an individual's risk to develop PACG. In addition, genetic factors have been identified that modify PACG endophenotypes for example, axial length. Herein we review the current literature on this important topic.
| S-EPMC4815686 | biostudies-literature
Project description:PurposeTo investigate the different impacts on patient-reported vision-related quality of life (pVRQOL) outcomes in patients with primary angle-closure glaucoma(PACG) and primary open-angle glaucoma(POAG).MethodsProspective cross-sectional study. PACG and POAG patients who had a best-corrected visual acuity(BCVA) in the better eye equal to or better than 20/60, intraocular pressure controlled at or below 25 mmHg and reliable visual field test were invited to participate. The control group included patients with BCVA in the better eye equal to or better than 20/60 and who did not have major eye disease. A validated Taiwanese version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25(T)) was performed to assess pVRQOL. The association between each domain of NEI VFQ-25(T) among 3 groups was determined using multivariable linear regression analysis.ResultsA total of 106 PACG, 186 POAG, and 95 controls were enrolled. In multivariable regression analysis of all three groups(PACG/POAG/controls), compared to POAG, PACG showed a weakly positive association with social functioning (R2 = 0.13, ? = 0.22, P = 0.04). PACG showed no significantly negative impact on pVRQOL compared to controls. Taking only glaucoma patients into consideration, PACG patients had a higher score on social functioning compared to POAG (R2 = 0.16, ? = 0.27, P = 0.01). The results of other domains of NEI VFQ-25(T) between the two groups did not differ significantly(p>0.05).ConclusionsIn patients with controlled disease, the impact of PACG and POAG on most domains of NEI VFQ-25(T) were similar, except for better social functioning in PACG compared to POAG.
| S-EPMC5045164 | biostudies-literature
Project description:Current estimates suggest 50% of glaucoma blindness worldwide is caused by primary angle-closure glaucoma (PACG) but the causative gene is not known. We used genetic linkage and whole genome sequencing to identify Spermatogenesis Associated Protein 13, SPATA13 (NM_001166271; NP_001159743, SPATA13 isoform I), also known as ASEF2 (Adenomatous polyposis coli-stimulated guanine nucleotide exchange factor 2), as the causal gene for PACG in a large seven-generation white British family showing variable expression and incomplete penetrance. The 9 bp deletion, c.1432_1440del; p.478_480del was present in all affected individuals with angle-closure disease. We show ubiquitous expression of this transcript in cell lines derived from human tissues and in iris, retina, retinal pigment and ciliary epithelia, cornea and lens. We also identified eight additional mutations in SPATA13 in a cohort of 189 unrelated PACS/PAC/PACG samples. This gene encodes a 1277 residue protein which localises to the nucleus with partial co-localisation with nuclear speckles. In cells undergoing mitosis SPATA13 isoform I becomes part of the kinetochore complex co-localising with two kinetochore markers, polo like kinase 1 (PLK-1) and centrosome-associated protein E (CENP-E). The 9 bp deletion reported in this study increases the RAC1-dependent guanine nucleotide exchange factors (GEF) activity. The increase in GEF activity was also observed in three other variants identified in this study. Taken together, our data suggest that SPATA13 is involved in the regulation of mitosis and the mutations dysregulate GEF activity affecting homeostasis in tissues where it is highly expressed, influencing PACG pathogenesis.
| S-EPMC7233598 | biostudies-literature
Project description:PurposeTo evaluate the association between baseline ocular variables and the widening of the anterior chamber angle by laser peripheral iridotomy (LPI) in primary angle closure suspects (PACS) using a new Fourier-domain swept-source anterior segment optical coherence tomography (FD-ASOCT).MethodSixty-six PACS eyes of 41 individuals were enrolled in this prospective interventional case series. An FD-ASOCT (Casia SS-1000 OCT; Tomey, Nagoya, Japan) was used to measure biometric baseline variables and at 1 month after the LPI. Paired t test was used to compare the difference between pre-and post-LPI measurements. Multivariate regression analysis was used to test for an association between baseline iris thickness and volume, anterior chamber depth and volume, and lens vault with a widening of the angle after an LPI. Changes in trabecular iris space area and angle opening distance after the LPI were main outcome measures.ResultsThe mean age of participants was 58.6 ± 8.7 years, 68.2% of whom were female. The angle opening distance, recess area, and trabecular iris surface area at 500 μm increased by 48 to 73% (all P < 0.001). Lens vault and iris volume did not change. A low anterior chamber volume and low iris volume were associated with angle greater deepening by LPI.ConclusionEyes with a shallow anterior chamber and thinner irises are more likely to experience angle opening from an LPI.
| S-EPMC7809532 | biostudies-literature