25-羟基维生素D3水平及其受体基因rs2228570 F/f位点多态性与深圳地区子宫内膜异位症遗传易感性分析

Analysis of 25-hydroxyvitamin D3 level and its receptor gene rs2228570 F/f polymorphism and genetic susceptibility to endometriosis in Shenzhen area

目的了解不同临床分期子宫内膜异位症(EMT)25-羟基维生素D3[25-(OH)VitD3]水平及与糖类抗原-125(CA125)和细胞因子的相关性及维生素D受体基因(VDR)rs2228570 F/f位点多态性,探讨其与深圳地区EMT遗传易感性。方法选择2021年5月至2023年1月在深圳市龙华区人民医院确诊EMT患者102例(EMT组),年龄19~46岁,平均年龄32.57岁;临床分期Ⅰ期19例,年龄19~40岁,平均年龄30.25岁;Ⅱ期27例,年龄19~42岁,平均年龄31.05岁;Ⅲ期35例,年龄20~44岁,平均年龄31.82岁;Ⅳ期21例,年龄21~46岁,平均年龄33.91岁。同期非EMT患者78例(对照组),年龄18~48岁,平均年龄31.82岁。分别检测25-(OH)VitD3、CA125、白细胞介素6(IL-6)及干扰素-γ(IFN-γ)水平,同时分析VDR rs2228570 F/f位点多态性。结果EMT组25-(OH)VitD3和IFN-γ水平[(11.38±3.37)ng/mL、(14.90±3.65)pg/mL]明显低于对照组[(18.86±1.41)ng/mL、(20.99±2.10)pg/mL],而CA125和IL-6水平[(36.08±12.49)U/mL和(27.00±10.82)pg/mL]明显高于对照组[(17.70±2.52)U/mL和(13.37±1.64)pg/mL],差异有统计学意义(P<0.05);EMT组25-(OH)VitD3和IFN-γ水平Ⅳ期<Ⅲ期<Ⅱ期<Ⅰ期,而CA125和IL-6水平Ⅳ期>Ⅲ期>Ⅱ期>Ⅰ期,不同临床分期之间差异有显著统计学意义(P<0.001);经相关分析,EMT组25-(OH)VitD3与CA125、IL-6水平及临床分期呈负相关,而与IFN-γ水平呈正相关(r=-0.6773,-0.6836、-0.7481、0.6951,P<0.05);EMT组ff基因型和f等位基因频率(61.76%和72.06%)明显高于对照组(17.95%和26.28%),而FF基因型和F等位基因频率(17.65%和27.94%)明显低于对照组(65.38%和73.72%),差异有统计学意义(P<0.05);但Ff基因型频率(20.59%vs 16.67%)差异无统计学意义(P>0.05),且不同临床分期EMT患者VDR rs2228570 F/f位点基因型和等位基因频率差异无统计学意义(P>0.05);不同基因型EMT患者25-(OH)VitD3水平存在差异(P<0.05),其中ff基因型25-(OH)VitD3水平[(9.30±2.15)ng/mL]明显低于Ff和FF基因型[(14.59±1.56)ng/mL、(15.14±1.85)ng/mL],差异有统计学意义(P<0.05);但FF与Ff基因型差异无统计学意义(P>0.05)。结论EMT患者25-(OH)VitD3水平明显降低,且与CA125、IL-6、IFN-γ水平及临床分期存在一定的相关性。同时VDR rs2228570 F/f位点分布呈多态性,其中ff基因型EMT患者25-(OH)VitD3水平更低,可能是导致深圳地区EMT发病的危险易感基因之一。

Objective To investigate the levels of 25-hydroxyvitamin D3[25-(OH)VitD3]in different clinical stages of endometriosis(EMT)and its correlation with carbohydrate antigen-125(CA125)and cytokines,polymorphism of vitamin D receptor gene(VDR)rs2228570 F/f locus,and explore its genetic susceptibility to EMT in Shenzhen area.Methods From May 2021 to January 2023,a total of 102 patients with EMT(EMT group)in Longhua District People’s Hospital,Shenzhen were enrolled,which aged 19-46 years old with mean age of 32.57 years old.There were 19 cases of clinical stageⅠ,aged 19-40 years old with mean age of 30.25 years old;27 of stageⅡ,aged 19-42 years old with mean age of 31.05 years old;35 of stageⅢ,aged 20-44 years old with mean age of 31.82 years old;21 of stageⅣ,aged 21-46 years old with mean age of 33.91 years old.At the same period,78 non-EMT patients were set as control group,which aged 18-48 years old with mean age of 31.82 years old.The levels of 25-(OH)VitD3,CA125,interleukin 6(IL-6)and interferonγ(IFN-γ)were detected,and polymorphism of VDR rs2228570 F/f locus was analyzed.Results The levels of 25-(OH)VitD3 and IFN-γin EMT group[(11.38±3.37)ng/mL,(14.90±3.65)pg/mL]were significantly lower than those in control group[(18.86±1.41)ng/mL,(20.99±2.10)pg/mL],while levels of CA125 and IL-6[(36.08±12.49)U/mL and(27.00±10.82)pg/mL]were significantly higher than those in control group[(17.70±2.52)U/mL and(13.37±1.64)pg/mL],and the differences were significant(P<0.05).The levels of 25-(OH)VitD3 and IFN-γin EMT group were stageⅣ<stageⅢ<stageⅡ<stageⅠ,while levels of CA125 and IL-6 were stageⅣ>stageⅢ>stageⅡ>stageⅠ,and the differences between different clinical stages were statistically significant(P<0.001).The correlation analysis results showed that 25-(OH)VitD3 in EMT group was negatively correlated with CA125,IL-6 levels and clinical stage,but positively correlated with IFN-γlevel(r=-0.6773,-0.6836,-0.7481,0.6951,P<0.05).The frequencies of ff genotype and f allele in EMT group(61.76%and 72.06%)were significantly higher than those in control group(17.95%and 26.28%),while frequencies of FF genotype and F allele in EMT group(17.65%and 27.94%)were significantly lower than those in control group(65.38%and 73.72%),and the differences were statistically significant(P<0.05).However,there was no significant difference in frequency of Ff genotype between the different groups(20.59%vs 16.67%.P>0.05),and there were no significant differences in genotype and allele frequency of VDR rs2228570 F/f locus for EMT patients with different clinical stages(P>0.05).The level of 25-(OH)VitD3 in EMT patients with different genotypes was different(P<0.05),the level of 25-(OH)VitD3 in ff genotype[(9.30±2.15)ng/mL]was significantly lower than that in Ff and FF genotypes[(14.59±1.56)ng/mL,(15.14±1.85)ng/mL],the difference was statistically significant(P<0.05),but there was no significant difference between FF and Ff genotypes(P>0.05).Conclusion It is demonstrated that the level of 25-(OH)VitD3 in EMT patients is significantly decreased,and there is a certain correlation with levels of CA125,IL-6,IFN-γand clinical stage.The distribution of VDR F/f locus rs2228570 shows polymorphism,and 25-(OH)VitD3 level is lower in ff genotype EMT patients,which may be one of the risk susceptibility genes leading to EMT in Shenzhen area.