| ObjectiveMyopia has become an important global public health problem due to its increasing prevalence.The prevalence of myopia among Chinese children and adolescents ranks in the highest level in the world,and myopia always have a great impact on the physical health of Chinese students.Currently,the etiology of myopia is still unclear,and the combined effects of both genetic and environmental factors are considered to lead to the occurrence and development of myopic refraction.However,at present,the study on myopia among children and adolescents in China mostly focuses on environmental factors.There are few studies on the genetic susceptibility of myopia in children and adolescents,and there is a lack of comprehensive analysis of the genetic and environmental factors of myopia in children and adolescents.The purpose of this study includes the following four aspects:?1?understanding the status of myopic refraction among children and adolescents in urban areas of Tianjin;?2?clarifying the environmental factors related to myopic refraction in children and adolescents,in order to provide practical and feasible measures for the prevention and control of myopia;?3?analyzing the polymorphism of susceptibility genes related to myopia in children and adolescents,in order to further reveal the possible pathogenesis of myopia and laying the foundation for genetic diagnosis of myopia;?4?integrating genetic and environmental factors on myopia,and putting forward the preliminary interpretation of genetic and environmental factors affecting myopia in children and adolescents,thus providing a scientific basis for the prevention and control of myopia among children and adolescents in China.Methods1.This was a cross-sectional study,using a stratified cluster random sampling method.From September to December 2016,two districts were randomly selected from the six main urban districts in Tianjin.One primary school and one junior high school were randomly chosen from each district.Then,one class was randomly selected from each grade within the selected schools.All children in the selected classes were invited to participate in this study voluntarily.Finally,566 children and adolescents aged 6-14 years old were included in our study.The comprehensive eye examination was performed by the professional ophthalmologists,using non-contact tonometer?Canon TX-20,Japan?to measure intraocular pressure and slit lamp to examine the fundus and anterior segment in order to rule out contraindications for cycloplegic agents.After cycloplegia?mydriasis?in children and adolescents,refraction measurements were performed with an auto-kerato-refractor?Canon RK-F1,Japan?to collect refractive status of children and adolescents.2.A case-control study was carried out to compare the differences of the situation in early life,family environment,habits with the eye,near work and outdoor activities between myopia group and non-myopia group,and to explore the environmental risk factors of myopia.3.Four genes,TGFB1,RASGRF1,CTNND2 and ZC3H11B,which may be associated with myopia and refractive development,were selected,including rs4803455,rs2241716,rs1800469,rs8027411,rs4778879,rs6885224,rs12716080,rs4428898 rs4373767,rs10779363 and rs7544369.The gene polymorphisms of 210non-myopic children and 343 myopic children were measured by TaqMan-PCR.The frequency distribution of each genotype and allele between the two groups was compared,and the linkage disequilibrium?LD?and haplotype analysis of LD were further carried out on genes associated with myopia.4.Genetic risk score?GRS?was used to evaluate the risk of individual myopic refraction caused by genetic factors,and to explore the effect of environmental and genetic factors on myopic refraction.After controlling the genetic background,the environmental risk factors related to myopia were screened out again,so as to take targeted prevention and control measures for myopia in children and adolescents.5.The statistical analysis was performed by SPSS 21.0.The Chi-square tests,t-tests,multiple logistic regression models and multiple linear regression models were used for statistical analysis according to the data characteristics.Haploview 4.2software was used for LD analysis and haplotype analysis of LD.Bonferroni correction for multi-group pairwise comparisons was performed.The test level is?=0.05.Results1.The prevalence of myopia in children and adolescents aged 6-14 years in urban areas of Tianjin was 62.2%?352/566?,and the spherical equivalent refraction?SER?was-1.31±1.85 D.The prevalence of myopia(c2trend=71.577)and SER?F=73.730?were statistically significant?P<0.001?among different age groups;however,there was no significant difference between the sexes?P>0.05?.Integrating the factors that statistically significant differences in the situation at birth,family environment,habits with the eye,near work and outdoor activities,we finally found that an older age?P<0.001?,a monthly family income of 10000-15000 RMB?P=0.007?and?15000 RMB?P=0.023?,often playing electronic devices when taking public transportation?P=0.040?and daily spent more time reading and writing?P=0.043?were risk factors for myopia.Breastfeeding?P<0.05?and no history of drinking during pregnancy?P=0.049?were protective factors for myopia.At the same time,age?P<0.001?,breastfeeding?P<0.05?,a monthly family income of10,000-15,000 RMB?P<0.001?,using LED lamp for homework?P=0.001?,sometimes reading in direct sunlight?P=0.010?,daily time spent reading and writing?P<0.001?and daily time spent using computers?P<0.001?were associated with SER in children and adolescents.2.SNPs rs4803455,rs1800469 in TGFB1 and rs4428898,rs4373767,rs10779363 and rs7544369 in ZC3H11B showed statistically significant differences in genotype and allele frequencies between non-myopia group and myopia group?P<0.05?.After adjusting for sex and age,the genotype distribution of rs4803455,rs1800469,rs4428898 and rs7544369 still differed significantly,and the allele distribution of rs1800469,rs4428898,rs4373767,rs10779363,rs7544369 also showed significantly differences.Distribution of three haplotypes?ATTC,GCCT and GCCC?composed of four SNPs in ZC3H11B was significantly different between non-myopia group and myopia group?P=0.015,P=0.003 and P=0.007,respectively?.After 50,000 permutation tests,this result remained significant.3.GRS was calculated for each subject.Under the condition of controlling the genetic background?after adjusting for GRS?,we found that age,breastfeeding,a higher monthly family income,often playing electronic devices when taking public transportation,sometimes reading in direct sunlight,daily spent more time reading and writing and daily spent more time using computers were still associated with the prevalence of myopia or SER?P<0.05?.Conclusions1.Our study found that the prevalence of myopia in children and adolescents aged 6-14 years in urban areas of Tianjin was still at a high level in 2016.The situation of prevention and control of myopia in children and adolescents was still very serious.2.Environmental factors such as the situation in early birth?breastfeeding?,family environment,habits with the eye,near work and outdoor activities could affect myopic refraction in children and adolescents.3.Our study suggested that genetic polymorphisms related to myopic refraction might affect the susceptibility of myopia in children and adolescents,but further studies are still needed to confirm.4.This study proposed that in the comprehensive analysis of the combined effects of genetic and environmental factors on myopia in children and adolescents,and combined with the genetic background of myopia in different individuals,the formulation of effective intervention strategies and interventions could protect visual health of children and adolescents to the greatest extent.It has important guiding significance for the prevention and control of myopia in Chinese children and adolescents. |
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