Dataset Information

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.

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.

SUBMITTER: Wang S

PROVIDER: S-EPMC6198425 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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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.

Wang Shaolin S Zhuang Wenjuan W Ma Jianqing J Xu Manyun M Piao Shunyu S Hao Juan J Zhang Wen W Chi Hao H Xue Zhongqi Z Ha Shaoping S

BMC ophthalmology 20181022 1

<h4>Background</h4>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 p ...[more]

PMID: 30348125

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Project description:PurposeWe sought to investigate anatomic mechanisms of angle narrowing by assessing ocular biometric determinants of anterior chamber angle width.DesignPopulation-based cross-sectional study.MethodsSubjects ≥50 years of age from the Chinese American Eye Study underwent a comprehensive ocular examination, including anterior segment optical coherence tomography imaging and ultrasound A-scan. Independent variables, including anterior chamber depth (ACD), lens vault (LV), iris curvature (IC), anterior chamber width, lens thickness, vitreous cavity depth, and axial length, and dependent variables, including angle opening distance, were measured in 1 randomly selected eye per subject. Univariable and multivariable regression models with standardized regression coefficients (SRCs) and semipartial correlation coefficients squares (SPCC2) were used to assess relative and unique contributions by independent variables to angle width.ResultsTwo thousand two hundred twenty-five subjects (1433 women and 834 men) were included in the analysis. All biometric parameters except lens thickness differed between men and women (age-adjusted P < .001). In model 1A (R2 = 0.66), which included ACD, lens thickness, and vitreous cavity depth, ACD (SRC = 0.64, SPCC2 = 0.19) and IC (SRC = -0.26, SPCC2 = 0.041) were the strongest determinants of angle opening distance. In model 1B (R2 = 0.58), which included LV and axial length, LV (SRC = -0.46, SPCC2 = 0.1) and IC (SRC = -0.3, SPCC2 = 0.047) were the strongest determinants of angle opening distance. Determinants of angle width were similar in separate multivariable models for men and women.ConclusionsACD, LV, and IC are the strongest determinants of angle width in Chinese Americans. Sex-related differences in angle width are explained by differences among biometric measurements. These results provide insights into anatomic mechanisms of angle narrowing and have important implications for quantitative assessments of angle closure eyes.

Project description:PurposeTo assess differences in ocular biometric measurements between primary angle closure suspect (PACS) eyes and primary angle closure (PAC) and primary angle closure glaucoma (PACG) eyes.DesignCross-sectional study.ParticipantsPatients with primary angle closure disease (PACD) were identified from the Chinese American Eye Study, a population-based study in Los Angeles, California.MethodsPatients previously underwent complete ocular examinations including gonioscopy and anterior segment (AS)-OCT imaging with the Tomey CASIA SS-1000 (Tomey Corporation). Four AS-OCT images were analyzed per eye. Averaged and sectoral measurements of biometric parameters, including angle recess area (ARA), trabecular iris space area (TISA), iris area, iris curvature, lens vault, anterior chamber depth, and anterior chamber area, were compared between early PACD (PACS) and late PACD (PAC and PACG) groups. Machine learning classifiers that attempt to differentiate between early and late PACD eyes were developed by applying different regression algorithms to a training dataset of sectoral parameter measurements. Classifier performance was assessed using an independent test dataset.Main outcome measuresAveraged and sectoral measurements of biometric parameters.ResultsTwo hundred ninety-eight eyes (231 PACS, 67 PAC or PACG) of 298 patients were analyzed. No difference was found in averaged biometric measurements between the 2 groups before (P > 0.09) or after (P > 0.14) adjusting for age and gender. Differences (P < 0.04) between the 2 groups were found for 11 sectoral parameter measurements, including ARA and TISA. The performance of machine learning classifiers developed using sectoral parameter measurements was poor on the independent test dataset for all regression algorithms (area under the receiver operating characteristic curve, 0.529-0.628).ConclusionsDifferences in biometric measurements between subtypes of PACD eyes were small in a population-based cohort of Chinese Americans. The poor performance of classifiers based on these measurements highlights potential challenges of developing quantitative methods to detect late PACD.

Dataset Information

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.

Publications

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.

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