IL-10启动子区基因多态性与神经梅毒的相关性研究

Association between Interleukin-10 Promoter Region Gene Polymorphism with Neurosyphilis

目的研究白细胞介素-10(IL-10)基因启动子区的多态性与神经梅毒发病风险的相关性。方法随机选择2013年4月~2016年8月期间笔者医院收治的150例梅毒患者作为研究组,其中包括48例神经梅毒患者和102例非神经梅毒患者,另招募同期在笔者医院门诊处的健康体检者150例作为对照组。采用Sanger测序法检测IL-10基因启动子中-592和-1082位点的SNP基因型,并分析-592和-1082位点的基因型与IL-10水平和神经梅毒发病风险之间的相关性。结果神经梅毒患者的CSF中IL-10水平明显比非神经梅毒患者高(7.94pg/ml vs 0.71pg/ml),差异有统计学意义(P<0.05)。研究组患者与对照组IL-10启动子区-592位点各基因型各等位基因频率和-1082位点的G、A等位基因频率以及单倍体G/C和A/A频率之间的差异均有统计学意义(P<0.05)。神经梅毒组患者IL-10启动子区-592位点的CC基因型频率和-1082位点的GG基因型频率明显比非神经梅毒组患者高,差异有统计学意义(P<0.05)。-1082位点GG基因型携带者患有神经梅毒的风险明显高于其他基因型携带者(OR=10.21,95%CI:1.94~53.04,P=0.001)。非神经梅毒组的患者中1082位点AA基因型频率明显高于梅毒患者组,差异有统计学意义(P<0.05)。-592位点CC基因型的携带者患神经梅毒的风险明显高于其他基因型携带者(OR=7.65,95%CI:1.38~42.55,P=0.004)。-1082/-592 G/C单倍体具有很高的神经梅毒患病风险(OR=45.14,95%CI:2.34~421.15,P=0.000)。-1082位点GG基因型的患者的CSF中IL-10水平明显比A等位基因携带者高,差异有统计学意义(8.15pg/ml vs 0.81pg/ml,P=0.000)。-592位点CC基因型、CA基因型和AA基因型患者CSF中的IL-10水平之间的差异无统计学意义(1.24pg/ml、1.00pg/ml和0.82pg/ml,P>0.05)。结论 IL-10基因启动子区的多态性与神经梅毒发病风险相关,携带-592C和-1082G等位基因的患神经梅毒的风险更高,脑脊液中IL-10水平也更高。

Objective To study the correlation between the polymorphism of interleukin-10（ IL-10） gene promoter region and the risk of neurosyphilis. Methods A total of 150 syphilis patients were enrolled in our hospital from April 2013 to August 2016 as the study group,including 48 neurosyphilis patients and 102 non-neurosyphilis patients. Another 150 health subjects were recruited as control group. SNP genotypes of-592 and-1082 loci in IL-10 gene promoter were detected by Sanger sequencing and the correlation between genotype at-592 and-1082 loci with IL-10 level and the risk of neurosyphilis were analyzed. Results The level of IL-10 in CSF of neurosyphilis patients was significantly higher than that in non-neurosyphilis patients（ 7. 94 pg/ml vs 0. 71 pg/ml）,the difference was statistically significant（ P〈0.05）. The differences of allele frequencies of each genotype in IL-10 promoter region-592 locus,the G and A allele frequencies and the haploid G/C and A/A gene frequencies between the study group and the control were statistically significant（ P〈0.05）. The frequency of CC genotype in IL-10 promoter region-592 locus and the frequency of GG genotype in the IL-10 promoter-1082 site of neurosyphilis group were significantly higher than those in the non-hypertensive group（ P〈0.05）. The risk of neurosyphilis was significantly higher in-1082 locus GG genotype carriers than in other genotype carriers（ OR = 10. 21,95% CI：1. 94-53. 04,P = 0. 001）. The frequencies of AA genotype in 1082 locus in neurosyphilis patients were significantly higher than those in syphilis group（ P〈0.05）. The risk of neurosyphilis was significantly higher in carriers of CC genotype at-592 locus than in other genotype carriers（ OR = 7. 65,95% CI： 1. 38-42. 55,P = 0. 004）.-1082/-592 G/C haplotypes had a high risk of neurosyphilis（ OR =45. 14,95% CI： 2. 34-421. 15,P = 0. 000）. The level of IL-10 in the CSF of GG genotype in-1082 locus was significantly higher than that of an allele carrier（ 8. 15 pg/ml vs 0. 81 pg/ml,P = 0. 000）. There was no significant difference in IL-10 levels between CC genotype,CA genotype,and AA genotype in CSF（ 1. 24 pg/ml,1. 00 pg/ml and 0. 82 pg/ml,P〈0.05）. Conclusion The polymorphism of IL-10 gene promoter region is associated with the risk of neurosyphilis,-592 C and-1082 G allele carriers have a higher risk of developing neurosyphilis and higher levels of IL-10 in cerebrospinal fluid.