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      Meta-Analysis of the Association between Lumican Gene Polymorphisms and Susceptibility to High Myopia

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          Abstract

          Backgrounds

          Many studies have evaluated the association between lumican (LUM) gene polymorphisms and high myopia. However, the results remain controversial. This meta-analysis aims to comprehensively evaluate the relationship between two common LUM polymorphisms (rs3759223 and rs3759222) and the risk of high myopia.

          Methods

          A comprehensive literature search for studies published up until September of 2013 was performed. Data were extracted independently by two investigators, and the weighted Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for the associations were obtained by using a random-effects model.

          Results

          Eight studies (1425cases and 1271 controls) were identified for the analysis of the association between rs3759223 polymorphism and high myopia. The results indicated that rs3759223 polymorphism was associated with high myopia under a recessive model (OR = 1.71, 95%CI 1.04–2.81). Further subgroup analysis indicated that this polymorphism was associated with high myopia among Chinese people in the additive model (OR = 1.17, 95%CI 1.06–1.29) and a recessive model (OR = 1.75, 95%CI 1.00–3.06) with control group coming from hospital based population. Four studies (1024 cases and 1163 controls) were identified for the analysis of the association between rs3759222 polymorphism and high myopia. The results indicated that rs3759222 polymorphism was not associated with high myopia in all genetic models, even the subgroup analysis couldn't provide relative proof to assure the outcome.

          Conclusion

          This meta-analysis suggests that LUM polymorphisms are associated with the risk of high myopia. However, well-designed studies with larger sample sizes and more ethnic groups are required to further validate this association.

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          Most cited references25

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          High prevalence of myopia and high myopia in 5060 Chinese university students in Shanghai.

          Myopia is an important cause of correctable visual impairment worldwide. Genetic and environmental factors contribute to its development. The population of Chinese university students consists of approximately 30 million young people characterized by academic excellence and similar ages. To date, little is known about their refractive status. Our study is designed to investigate the prevalence of myopia in this specific population. This is a cross-sectional study of myopia among university students in Shanghai, China; 5083 students from Donghua University were enrolled. All participants first responded to a detailed questionnaire, including questions on ethnicity, birth date, and family history, and then undertook a standardized ophthalmologic examination, including visual acuity, a slit-lamp examination, and non-cycloplegic autorefraction. The mean spherical equivalent refraction (SER) of the university students was -4.1 diopters (D). Of the subjects 95.5% were myopic (SER < -0.50 D), 19.5% were highly myopic (SER < -6.0 D), and only 3.3% were emmetropic (-0.5 D ≤ SER ≤ 0.5 D). The postgraduates were more myopic than the undergraduates (96.9% and 94.9%, respectively). Being female (-4.1 ± 2.4 D in female versus -3.8 ± 2.4 D in male subjects), of Han ethnicity (-4.1 ± 2.4 D in Han versus -3.4 ± 2.2 D in minorities), and of older age were associated with a higher probability of myopia only in the undergraduate population. The prevalence of myopia and high myopia in this university student population was high. The refractive status of this population deserves further attention.
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            Axial Length of Myopia: A Review of Current Research

            Myopia, or nearsightedness, is a worldwide common type of refractive error. It is a non-life-threatening disorder with huge social and economic consequences due to its increasing prevalence. Axial length (AL) is the primary determinant of non-syndromic myopia. It is a parameter representing the combination of anterior chamber depth, lens thickness and vitreous chamber depth of the eye. AL can also be treated as an endophenotype of myopia and may provide extra advantages in the investigation of its genetic basis. The study of AL will not only identify the determinants of eye elongation, but also provide aetiological evidence for myopia. The purpose of this review is to outline the current state of AL research. Epidemiological evidence, genetic determinants, the relationship with other eye components and relative animal models of AL are summarised.
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              Myopia over the lifecourse: prevalence and early life influences in the 1958 British birth cohort.

              To investigate the hypothesis that the excessive growth of the eye in myopia is associated with general growth and thus influenced by early life biological and social factors, and that these associations underlie recent secular trends of increasing prevalence and severity of myopia. Cohort study. A total of 2487 randomly selected 44-year-old members of the 1958 British birth cohort (27% subsample). Diverse and detailed biological, social, and lifestyle data have been collected by following members since birth through a series of clinical examinations or face-to-face interviews carried out by trained examiners. At 44 years, cohort members underwent autorefraction using the Nikon Retinomax 2 (Nikon Corp., Tokyo, Japan) under non-cycloplegic conditions. A lifecourse epidemiologic approach, based on 4 sequential multivariable "life stage" models (preconceptional; prenatal, perinatal, and postnatal; childhood; and adult), was used to examine the influence of early life biological, social and lifestyle factors, growth patterns, and "eye-specific" factors on myopia. Myopia severity (all, mild/moderate: spherical equivalent -0.75 to -5.99 diopters [D]; severe: ≥-6.00 D extreme vs. emmetropia -0.74 to +0.99 D) and myopia onset (early [<16 years] vs. later). A total of 1214 individuals (49%; 95% confidence interval, 48.8-50.8) were myopic (late onset in 979 [80.6%]). Myopia was positively associated with low birthweight for gestational age, gender, greater maternal age, higher paternal occupational social class, and maternal smoking in early pregnancy. Myopia was independently associated with proxy markers of near work and educational performance, with some differences by onset and severity. In adults, greater height and higher educational attainment and socioeconomic status were associated with myopia. Trends in the key influences on child health and growth identified as novel putative risk factors in this study are consistent with global trends of increasing myopia: increasing births to older mothers, increasing rates of intrauterine growth retardation and survival of affected children, increasing persistence of smoking in pregnancy, and changing socioeconomic status. Prospects for prevention of myopia would be improved by a paradigm shift in myopia research, with lifecourse and genetic epidemiologic approaches applied in tandem in large unselected populations. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                23 June 2014
                : 9
                : 6
                : e98748
                Affiliations
                [1]Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, People's Republic of China
                Casey Eye Institute, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MH WW WH. Performed the experiments: MH WW. Analyzed the data: MH WW. Contributed reagents/materials/analysis tools: MH WW WH DR. Wrote the paper: MH WW.

                Article
                PONE-D-13-54639
                10.1371/journal.pone.0098748
                4067286
                24956166
                503d144d-5a38-4c44-9899-059928d044b3
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 December 2013
                : 6 May 2014
                Page count
                Pages: 7
                Funding
                This research was supported by the Scientific and Technology Foundation of Guangdong Province (2011B061300049, 2008B030301126). No additional external funding was received. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Sensory Systems
                Visual System
                Sensory Perception
                Medicine and Health Sciences
                Epidemiology
                Genetic Epidemiology
                Health Care
                Environmental Health
                Ophthalmology
                Eye Diseases
                Glaucoma
                Corneal Disorders
                Macular Disorders
                Pediatric Ophthalmology
                Public and Occupational Health
                Preventive Medicine
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Research and Analysis Methods
                Research Design
                Clinical Research Design

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