染色体15q14、15q25和13q12.12区域单核苷酸多态性与宁夏回族、汉族高度近视的相关性研究

背景 目前认为高度近视是多基因遗传性眼病,其发病受遗传因素及环境因素的共同作用,具有显著的遗传异质性.已有研究报道了高度近视相关的候选基因,但后续的研究中一些候选基因与高度近视的关系仍存在争议. 目的 研究已有报道的染色体15q14、15q25和13q12.12区域单核苷酸多态性（SNPs）与中国宁夏地区回族、汉族高度近视人群的关联性.方法 纳入2011年10月至2013年1月在宁夏眼科医院及宁夏医科大学总医院眼科就诊的高度近视患者487例进入前瞻性队列研究,包括汉族患者380例,回族患者107例,同期收集488名屈光状态和眼轴长度在正常范围的正常受检者作为对照,包括汉族受检者361例,回族受检者127例.收集所有受检者的外周血各5 ml,提取全血DNA,选取染色体15q14、15q25和13q12.12区域的rs634990、rs524952、rs8027411、rs9318086、rs9510902、rs3794338、rs1886970、rs7325450和rs7331047共9个标签SNPs,通过Sequenom质谱平台对受检者的各SNPs基因型进行测定,并对汉族高度近视组与正常对照组、回族高度近视组与正常对照组、汉族患者与回族患者间的基因型和等位基因分布进行比较,分析其与高度近视的相关性. 结果 汉族高度近视组与正常对照组位于染色体15q25区段的rs8027411SNPs基因型频率及等位基因频率的比较差异均有统计学意义（P=0.003、0.001）,GT和TT基因型优势比（OR）值分别为1.794（95％CI∶1.198 ～ 2.687）和1.697（95％ CI∶1.214～2.372）.回族与汉族高度近视患者间15q25区段的rs8027411位点等位基因频率的比较差异有统计学意义（P=0.038）,T等位基因OR值为0.725（95％CI∶0.534 ～0.983）.回族高度近视患者与正常对照者间在上述9个SNPs中的基因型频率及等位基因频率分布差异均无统计学意义（P＞0.05）. 结论 染色体15q25区段的rs8027411 SNPs可能与宁夏地区汉族高度近视的发病关联性较强.在rs8027411位点,携带GT和TT基因型的个体患高度近视的风险明显增加.本研究未发现上述9个SNPs与宁夏地区回族高度近视患者发病有关联.

Associations of single nucleotide polymorphisms of chromosomes 15q14,15q25 and 13q12.12 regions with high myopic eyes in Hui and Han population of Chinese Ningxia area

Background The cause of high myopia is not fully understood.It has been shown that environmental factors and genetic factors contribute to the development of high myopia and has genetic heterogeneity.Many candidate genes associated with high myopia have been reported.However,most of these associated candidate genes are controversial in subsequent studies.Objective This study was to investigate whether there are associations of genetic variations in chromosome 15q14,15q25,13q12.12 regions recently shown to confer risk of myopia in Hui and Han ethnicity populations of Chinese Ningxia area.Methods Four hundred and eighty-seven high myopia patients with 380 ethnic Han and 107 ethnic Hui as well as 488 ethnicity-and gender-matched normal subjects were included in this prospective cohort study.Periphery blood 5 ml was collected from all subjects.Nine tag single nucleotide polymorphisms （SNPs） including rs634990,rs524952,rs8027411,rs9318086,rs9510902,rs3794338,rs1886970,rs7325450 and rs7331047 across candidate chromosome on 15q14,15q25,13q12.12 regions were genotyped with MassArray and MALDI-TOF technique by Sequenom platform.The genotype and allele frequencies of the SNPs between the high myopia patients and normal controls were evaluated and compared by chisquared analysis,Mantel-Haenszel test and regression analysis.Results Significant differences were detected in genotype frequencies and allele frequencies of SNP rs8027411 in chromosome 15q25 between high myopia patients and normal subjects in the H an population （P =0.003,0.001）,and the odds ratio（OR） values of GT and TT genotype were 1.794 （95% CI∶ 1.198-2.687） and 1.697 （95% CI∶ 1.214-2.372）.The allele frequencies of SNP rs8027411were significant different in the individuals with high myopia between the Han and Hui population （P=0.038）,and the OR value of T allele was 0.725 （95% CI∶ O.534-0.983）.Conclusions Of the nine SNPs screened,the genotypes and alleles rs8027411 in the 15q25 region seem to be responsible for high myopia in the Han group but not the Hui group of Ningxia region.The risk for high myopia increases in the individuals with genotype of GT and TT in SNPs rs8027411.