摘要目的 研究增生性糖尿病视网膜病变(PDR)的遗传易感性.方法 采用横断面研究设计,纳入2011年9月至2012年2月在东莞眼病研究中确诊的2型糖尿病患者和2017年7月至2018年3月在广东省人民医院眼科诊治的相关患者共220例,其中100例糖尿病患者和120例PDR患者.采用全外显子组测序技术对22例不伴视网膜病变的2型糖尿病患者(糖尿病组)和23例PDR患者(PDR组)的外周血样本DNA进行单核苷酸多态性(SNP)、InDel等鉴定,筛选出其中具有显著差异的9个外显子区域位点,采用SnaPshot技术对78例不伴视网膜病变的2型糖尿病患者和97例PDR患者进行9个位点的SNP分型,并分析其单倍型和连锁不平衡性.结果 全外显子组测序检出75个位点SNP与PDR相关联(P＜0.01),涉及53个基因,其中11个位点位于外显子区,7个突变属于非同义突变.SnaPshot SNP分型技术验证其中9个显著差异的位点,发现其等位基因及基因型频率在PDR组和糖尿病组中差异无统计学意义(P＞0.05),但7种单倍型分布频率差异有统计学意义(P＜0.01),其中Hapl和Hap4可能会降低PDR的患病风险[均比值比(OR)＜1,P＜0.05)],Hap2可能会增加PDR的患病风险(OR＞1,P＜0.05). 结论 华南地区汉族2型糖尿病患者PDR的发生存在遗传易感性.

abstractsObjective To research the genetic susceptibility of proliferative diabetic retinopathy (PDR) in Han patients with type 2 diabetes from Southern China.Methods A cross-sectional study was performed under the informed consent of the patients.Patients with type 2 diabetes in the Dongguan Eye Study from September 2011 to February 2012 and relative patients treated in Guangdong General Hospital from July 2017 to March 2018 were included in this study,including 100 patients with diabetes mellitus(DM) and 120 patients with PDR.Whole exome sequencing was used to identify DNA mutation in peripheral blood samples from 22 type 2 diabetic patients without retinopathy (DM group) and 23 diabetic patients with PDR (PDR group).Genotype and allele of the nine selected single-nucleotide polymorphisms (SNPs) were tested and analyzed by SnaPshot technology in another 78 DM patients without retinopathy and 97 PDR patients.Results A total of 75 SNPs were associated with PDR (P＜0.01),involving 53 genes.Eleven gene loci were in the exon region and 7 were non-synonymous mutations.Nine exon loci of 8 genes with significant differences were screened out for the verification.SnaPshot SNP genotyping technique found that there were no significant differences in allele and genotype frequency in the nine selected SNPs between PDR group and DM group (all at P＞0.05).However,7 haplotypes distribution frequencies were significantly different between PDR group and DM group (all at P＜0.01).Hapl and Hap4 might reduce the risk of PDR (both at OR＜1,P＜0.05),and Hap2 might increase the risk of PDR (OR＞ 1,P＜0.05).Conclusions The occurrence of PDR probably has a genetic susceptibility in type 2 DM patients of Han nationality in Southern China.