2型糖尿病视网膜病变患者血清中VitD水平及VDR基因rs2228570F/f位点多态性分析

Analysis the level of VitD and VDR gene rs2228570F/f polymorphism in patients with type 2 diabetic retinopathy

目的了解深圳地区2型糖尿病视网膜病变(DR)患者血清中25羟基维生素D3[25-(OH)VD3]水平表达情况,并探讨VitD受体(VDR)基因rs2228570F/f位点多态性与DR发病的易感性。方法选择2016年3月~2018年11月来深圳市眼科医院就诊并确诊为2型糖尿病(type2diabetesmellitus,T2DM)患者216例,其中单纯2型糖尿病83例为T2DM组、非增殖性视网膜病变71例为NPDR组及增殖性视网膜病变62例为PDR组,同时选取健康人群120例为对照组,采用化学发光法检测血清中25-(OH)VD3水平,同时采用PCR-RFLP法对VDR基因rs2228570F/f位点多态性进行分析,并对结果进行统计分析。结果NPDR组和PDR组患者血清中25-(OH)VD3水平分别为25.28±7.31nmol/L和的22.95±6.22nmol/L,差异无统计学意义(t=1.0652,P>0.05),但明显低于T2DM组患者的37.15±10.87nmol/L和对照组的54.09±13.72nmol/L,差异均有统计学意义(t=3.7185~7.3724,P<0.05);PDR组患者ff基因型及f等位基因频率分别为72.58%和83.06%,略高于NPDR组的70.42%和81.69%,差异无统计学意义(χ~2=0.7165~1.1044,P>0.05),但明显高于T2DM组的49.40%和67.47%,差异有统计学意义(χ~2=9.8063~10.7251,P<0.05),而T2DM组与对照组之间差异无统计学意义(χ~2=1.2029~1.4245,P>0.05);VDR基因rs2228570位点ff基因型DR患者血清中25-(OH)VD3水平为17.25±5.06nmol/L,明显低于Ff和FF基因型的23.98±5.82nmol/L和27.66±7.87nmol/L,差异有统计学意义(t=2.5032~3.0217,P<0.05);FF,Ff及ff基因型的DR发病率分别为42.86%,49.15%及69.86%,ff基因型的DR发病率明显高于FF和Ff基因型,差异有统计学意义(χ~2=7.6256~9.8542,P<0.05),而FF和Ff基因型的DR发病率之间差异无统计学意义(χ~2=1.1084~1.3927,P>0.05)。结论深圳地区DR患者血清中25-(OH)VD3水平缺乏严重,而VDR基因rs2228570位点ff基因型及f等位基因频率明显升高,且ff基因型的DR患者血清中25-(OH)VD3水平缺乏更为严重,DR发病率更高。因此,VDR基因rs2228570位点多态性突变可能与深圳地区DR发病有一定的相关性。

Objective:To investigate the expression of 25 hydroxyvitamin D3[25-(OH)VD3]in serum of type 2 diabetic retinopathy(DR)patients in shenzhen,and to investigate the polymorphism of VitD receptor(VDR)gene rs2228570 F/f site and the susceptibility to DR.Methods:From March 2016 to November 2018,216 patients with type 2 diabetes mellitus(T2 DM)were admitted to shenzhen eye hospital and diagnosed,Among them,83 cases of pure type 2 diabetes mellitus were in the T2 DM group,71 cases of non-proliferative retinopathy mellitus were in the NPDR group and 62 cases of proliferative retinopathy mellitus were in the PDR group,and 120 cases of healthy people were selected as the control group at the same time,by using chemiluminescence detection level of 25(OH)VD3 in serum,The polymorphism of VDR gene rs2228570 F/f site was analyzed by PCR-PFLP,and the results were statistically analyzed.Results:The levels of 25-(OH)VD3 in the NPDR group and PDR group were 25.28±7.31 nmol/L and 22.95±6.22 nmol/L,respectively,with no statistical significance(t=1.0652,P>0.05),but significantly lower than 37.15±10.87 nmol/L in the T2 DM group and 54.09±13.72 nmol/L in control group,with statistical significance(t=3.7185~7.3724,P<0.05).ff genotype and f allele frequency in PDR patients were 72.58%and 83.06%,slightly higher than 70.42%and 81.69%in the NPDR group,the difference was no statistically significant(χ~2=0.7165~1.1044,P>0.05),but significantly higher than 49.40%and 67.47%in T2 DM group,the difference was statistically significant(χ~2=9.8063~10.7251,P<0.05),while the T2 DM group and the control group there was no statistically significant difference between(χ~2=1.2029~1.4245,P>0.05);The level of 25-(OH)VD3 in VDR patients with ff genotype at rs2228570 was 17.25±5.06 nmol/L,significantly lower than 23.98±5.82 nmol/L and 27.66±7.87 nmol/L in Ff and ff genotypes,and the difference was statistically significant(t=2.5032~3.0217,P<0.05).The incidence of FF,Ff and ff genotypes were 42.86%,49.15%and69.86%,respectively.The incidence of ff genotypes was significantly higher than FF and Ff genotypes,with statistically significant difference(χ~2=7.6256~9.8542,P<0.05),while the incidence of FF and Ff genotypes had no statistically significant difference(χ~2=1.1084~1.3927,P>0.05).Conclusion:The level of 25-(OH)VD3 in DR patients in shenzhen area is seriously deficient,while the ff genotype and f allele frequency of VDR gene rs2228570 are significantly increased,and the level of 25-(OH)VD3 in DR patients with ff genotype is more seriously deficient and the incidence of DR is higher.Therefore,polymorphic mutation at rs2228570 of VDR gene may be correlated with the incidence of DR in shenzhen area.