Yanxian Chen

Association of estrogen receptor α gene polymorphisms with bone mineral density in Chinese women: a meta-analysis

Introduction and hypothesisA large number studies have examined the association between estrogen receptor alpha (ESR-α) gene polymorphisms and bone mineral density (BMD) in the Chinese population. We conducted a meta-analysis to assess their pooled effects.MethodsWe searched for all published articles indexed in MEDLINE, the Chinese Biomedical Database, and the Chinese Journal Full-text Database from January 1994 to April 2006. Any cross-sectional study that tested the association between ESR-α PvuII or XbaI genotypes and BMD at the femoral neck or spine in Chinese women was included in the review. Data were extracted independently by two reviewers using a standardized data extraction form. Sixteen eligible studies involving 4,297 Chinese women were identified.ResultsThe overall frequencies of X and P alleles were 28% and 40%, respectively. The PvuII polymorphism was statistically significantly associated with BMD at the femoral neck (P = 0.038 for PP = Pp = pp) but not at the lumbar spine in all women. The BMD difference for the contrasts of PP versus Pp/pp genotypes was −0.0105 (95%CI, −0.0202 ∼ −0.0008) g/cm2 (P = 0.036). The XbaI polymorphism was not associated with BMD at the femoral neck or lumbar spine.ConclusionThe PvuII polymorphism had a very weak association with femoral neck BMD whereas XbaI polymorphism was unlikely to be a predictor of femoral neck or spine BMD in Chinese women.

Comprehensive Mutation Analysis by Whole-Exome Sequencing in 41 Chinese Families With Leber Congenital Amaurosis

PURPOSE Leber congenital amaurosis (LCA) is a genetically heterogeneous disease with, to date, 19 identified causative genes. Our aim was to evaluate the mutations in all 19 genes in Chinese families with LCA. METHODS LCA patients from 41 unrelated Chinese families were enrolled, including 25 previously unanalyzed families and 16 families screened previously by Sanger sequencing, but with no identified mutations. Genetic variations were screened by whole-exome sequencing and then validated using Sanger sequencing. RESULTS A total of 41 variants predicted to affect protein coding or splicing was detected by whole-exome sequencing, and 40 were confirmed by Sanger sequencing. Bioinformatic and segregation analyses revealed 22 potentially pathogenic variants (17 novel) in 15 probands, comprised of 3 of 16 previously analyzed families and 12 of 25 (48%) previously unanalyzed families. In the latter 12 families, mutations were found in CEP290 (three probands); GUCY2D (two probands); and CRB1, CRX, RPE65, IQCB1, LCA5, TULP1, and IMPDH1 (one proband each). Based on the results from 87 previously analyzed probands and 25 new cases, GUCY2D, CRB1, RPGRIP1, CEP290, and CRX were the five most frequently mutated genes, which was similar to the results from studies in Caucasian subjects. CONCLUSIONS Whole-exome sequencing detected mutations in the 19 known LCA genes in approximately half of Chinese families with LCA. These results, together with our previous results, demonstrate the spectrum and frequency of mutations of the 19 genes responsible for LCA in Han Chinese individuals. Whole-exome sequencing is an efficient method for detecting mutations in highly heterogeneous hereditary diseases. Chinese Abstract.

The Guangzhou twin project: An update

The Guangzhou Twin Registry is a population-based registry of twins residing in Guangzhou City. The initial registry database included 9,700 pairs of young twins recruited from the Official Household Registry of Guangzhou City. The registry is designed to provide a resource to identify the genetic and environmental causes of common diseases with an initial focus on eye diseases. From 2006 onward, phenotype and DNA collection have been completed for more than 1,200 twin pairs and their parents or siblings. Most of the young twins have come back for an annual examination of the progressive traits, such as refraction, ocular biometry, weight, and height. Genome-wide association scans have been completed recently. This article gives an update of the study design, cohort profile, previous findings, and future directions. Results from the Guangzhou Twin Project may contribute to the understanding of gene-environmental interplay for complex diseases in both adults and children.

Methodology of the ZOC-BHVI High Myopia Cohort Study: The Onset and Progression of Myopic Pathologies and Associated Risk Factors in Highly Myopic Chinese

ABSTRACT Purpose: The increasing prevalence of high myopia and its associated pathologies has raised challenges to ophthalmic services. This project aims to explore the onset and progression of myopic pathologies in highly myopic eyes through a prospective research cohort established in South China. Methods: Patients with high myopia (sphere ≤ −6.00 D) visiting the optometric clinic of Zhongshan Ophthalmic Center (ZOC) were invited to participate in the baseline examinations and follow-up visit over a 10-year period. People having secondary myopia, history of any refractive surgery, significant ocular media opacity, or other severe health problems were excluded. The measurements included visual acuity, ocular biometry, visual function, cycloplegic refraction, fundus imaging, ocular shape by MRI, blood tests and questionnaires. Results: A total of 890 participants completed the baseline examinations, with a mean age at baseline of 22.7 ± 12.4 years. The mean spherical equivalent at baseline was 10.13 ± 3.65 D, and the mean axial length (AL) was 27.52 ± 1.63 mm. The older subjects tended to have more severe myopia and longer ALs. Conclusion: The study will provide new knowledge on the relationship between high myopia and pathological changes such as myopic macular degeneration and staphyloma.

Patterns in longitudinal growth of refraction in Southern Chinese children: cluster and principal component analysis

In the present study we attempt to use hypothesis-independent analysis in investigating the patterns in refraction growth in Chinese children, and to explore the possible risk factors affecting the different components of progression, as defined by Principal Component Analysis (PCA). A total of 637 first-born twins in Guangzhou Twin Eye Study with 6-year annual visits (baseline age 7–15 years) were available in the analysis. Cluster 1 to 3 were classified after a partitioning clustering, representing stable, slow and fast progressing groups of refraction respectively. Baseline age and refraction, paternal refraction, maternal refraction and proportion of two myopic parents showed significant differences across the three groups. Three major components of progression were extracted using PCA: “Average refraction”, “Acceleration” and the combination of “Myopia stabilization” and “Late onset of refraction progress”. In regression models, younger children with more severe myopia were associated with larger “Acceleration”. The risk factors of “Acceleration” included change of height and weight, near work, and parental myopia, while female gender, change of height and weight were associated with “Stabilization”, and increased outdoor time was related to “Late onset of refraction progress”. We therefore concluded that genetic and environmental risk factors have different impacts on patterns of refraction progression.

Identifying Children at Risk of High Myopia Using Population Centile Curves of Refraction

Purpose To construct reference centile curves of refraction based on population-based data as an age-specific severity scale to evaluate their efficacy as a tool for identifying children at risk of developing high myopia in a longitudinal study. Methods Data of 4218 children aged 5–15 years from the Guangzhou Refractive Error Study in Children (RESC) study, and 354 first-born twins from the Guangzhou Twin Eye Study (GTES) with annual visit were included in the analysis. Reference centile curves for refraction were constructed using a quantile regression model based on the cycloplegic refraction data from the RESC. The risk of developing high myopia (spherical equivalent ≤ -6 diopters [D]) was evaluated as a diagnostic test using the twin follow-up data. Results The centile curves suggested that the 3rd, 5th, and 10th percentile decreased from -0.25 D, 0.00 D and 0.25 D in 5 year-olds to -6.00 D, -5.65D and -4.63 D in 15 year-olds in the population-based data from RESC. In the GTES cohort, the 5th centile showed the most effective diagnostic value with a sensitivity of 92.9%, a specificity of 97.9% and a positive predictive value (PPV) of 65.0% in predicting high myopia onset (≤-6.00D) before the age of 15 years. The PPV was highest (87.5%) in 3rd centile but with only 50.0% sensitivity. The Mathew’s correlation coefficient of 5th centile in predicting myopia of -6.0D/-5.0D/-4.0D by age of 15 was 0.77/0.51/0.30 respectively. Conclusions Reference centile curves provide an age-specific estimation on a severity scale of refractive error in school-aged children. Children located under lower percentiles at young age were more likely to have high myopia at 15 years or probably in adulthood.

What Twin Studies Have Taught Us About Myopia.

AbstractMyopia has become epidemic, particularly in East Asia, and is a major cause of visual impairment worldwide. Twin studies are an important resource to investigate the genetics and the gene-environment interaction in myopia. This article aims to provide an overview of major findings regarding myopia from different types of twin studies, from the heritability of myopia-related traits to novel findings of genome-wide association studies. In the postgenomic era, twin studies will continue to serve as a unique method in the investigation of gene-environment interaction.

Incidence of and Factors Associated With Myopia and High Myopia in Chinese Children, Based on Refraction Without Cycloplegia

Importance Myopia has reached epidemic levels among children in regions of East and Southeast Asia. High myopia is associated with myopic macular degeneration, glaucoma, and retinal detachment. Objective To determine the incidence of myopia and high myopia based on refraction without cycloplegia among children in primary and junior high schools in China. Design, Setting, and Participants This observational cohort study was completed in Guangzhou, China. It consisted of a cohort from 19 primary schools, who were followed up from 2010 to 2015, and a cohort from 22 junior high schools, who were followed up from 2010 to 2012. All schools were randomly chosen at rates proportional to the number of schools in each of the city’s 11 districts. Students with or without myopia in grade 1 (primary school) or grade 7 (junior high school) were eligible for inclusion. Data analysis occurred from February 2017 to October 2017. Main Outcomes and Measures Myopia was defined as a spherical equivalent refraction (SER) of −0.50 diopters (D) or less, as measured by subjective refraction without cycloplegia; high myopia was defined as a SER of −6.0 D or less. Annual incidences were defined as the proportion of participants each year found to have myopia or high myopia who did not previously have the condition. Height, weight, axial length (AL), corneal radius of curvature (CRC), and AL/CRC ratio were examined to assess if these measures were associated with future myopia or high myopia. Results A total of 4741 students with or without myopia in either grade 1 for the primary school cohort (mean [SD] age 7.2 [0.4] years; 932 of 1975 [47.2%] female) or grade 7 for the junior high school cohort (mean [SD] age 13.2 [0.5] years; 1254 of 2670 [47.0%] female) were included. Baseline mean (SD) SER was 0.31 (0.86) D among 1975 students in grade 1 vs −1.60 (2.00) D among 2670 students in grade 7. Baseline prevalence of myopia was 12.0% in grade 1 students (n = 237 of 1969) and 67.4% in grade 7 students (n = 1795 of 2663). The incidence of myopia was 20% to 30% each year throughout both cohorts. The incidence of high myopia was initially less than 1% in the primary school cohort (grade 1: n = 2 of 1825; 0.1% [95% CI, 0.0%-0.3%]), but incidence exceeded 2% in the junior high school cohort (in grade 9: n = 48 of 2044; 2.3% [95% CI, 1.0%-3.7%]). Conclusions and Relevance The incidence of myopia among Chinese students based on refraction without cycloplegia is among the highest of any cultural or ethnic group. If confirmed with cycloplegic refraction, interventions to prevent myopia onset in Chinese populations should be initiated in primary schools.

Qualitative and quantitative assessment of posterior segment optical coherence tomography images using standard photos: the Liwan Eye Study.

Background/aims To develop a standardised grading scheme, using standard photos, for spectral-domain ocular coherence tomography (SD-OCT) images of the posterior eye and evaluate the interobserver agreement among trained ophthalmologists in identifying pathological changes. Methods Subjects were recruited from Liwan District, Guangzhou, with SD-OCT data collection from June 2013 to November 2013 as part of 10-year follow-up visits from the Liwan Eye Study. All subjects underwent SD-OCT imaging of the macula with scanning lines analysed by two ophthalmologists to assess for the presence of 12 different posterior segment lesions. Per cent agreement for each lesion between the graders and quantitative measures of dome-shaped macula (DSM) height and choroidal thickness were calculated. Results A total of 679 SD-OCT images from 679 subjects were independently evaluated by the two graders. Each of the 12 lesions was successfully graded as present or absent in over 96% of images. For all lesions, per cent agreement between observers was over 90%, ranging from 90.7% for epiretinal membranes and retinal pigment epithelium thickenings to 99.7% for full thickness macular holes and retinal detachments. Quantitative measurements of DSM height and choroidal thickness at three locations of the eye all exhibited intraclass correlation scores between the two graders of greater than 0.9. Conclusion Our study demonstrates high concordance between graders in characterising posterior segment lesions using SD-OCT images, validating the continued use of this imaging modality in the diagnosis of posterior eye disease.