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目的分析IL-12B基因3′非翻译区(UTR)+1188(A/C)位点单核苷酸多态性(SNP)与HBV宫内感染易感性的关系,探讨高危儿童发生宫内HBV感染的易感因素。方法母亲为HBV携带[HBsAg和(或)HBeAg阳性,或HBV DNA阳性]所生新生儿,出生后按程序进行主、被动联合免疫,出生时外周静脉血HBsAg和(或)HBV DNA阳性,并持续6个月以上者为宫内感染组,共70例;出生时及后期随访中未出现过HBsAg和(或)HBV DNA阳性,1岁时抗-HBs达保护滴度(>10 mU/L)者为宫内未感染组,71例;另取健康儿童外周血共40份作为对照。提取外周血基因组DNA,PCR扩增目的片段后进行测序,检测IL-12B基因3′UTR+1188(A/C)位点SNP。结果宫内感染组IL-12B基因+1188位点AA、AC、CC基因型分布频率分别为25.7%、44.3%和30.0%,宫内未感染组三种基因型分布频率为36.6%、47.9%和15.5%,正常对照组三种基因型的分布频率分别为48.8%、39.0%和12.2%。宫内感染组与宫内未感染组间CC基因型和非CC基因型之间频率分布差异有统计学意义(X~2=17.078,P<0.01,OR_(cc)=2.338,95%CI:1.028～5.035);三组等位基因频率分别为A 47.8%、60.7%和67.8%;C 52.2%、39.3%和32.2%,宫内感染组与宫内未感染组等位基因频率比较,无异有统计学意义(X~2=4.586,P=0.032;OR_A=0.597,95%CI:0.372～0.959;OR_C=1.673,95%CI:1.043～2.684)。结论IL-12B+1188位点A/C多态性CC基因型及C等位基因携带高危儿童可能易发生HBV宫内感染,而对携带HBV母亲所生的高危儿A等位基因可能对发生HBV宫内感染有一定的保护作用。
Objective To analyze the relationship between single nucleotide polymorphism (SNP) at 3 ’untranslated region (UTR) +1188 (A / C) locus and HBV intrauterine infection susceptibility in high-risk infants Susceptibility to infection. Methods The mothers were infants born with HBV [HBsAg and / or HBeAg positive or HBV DNA positive], and were given primary and passive combined immunization after birth. HBsAg and / or HBV DNA were positive at birth and There were 70 cases with intrauterine infection for more than 6 months. No HBsAg and / or HBV DNA were detected at birth and at follow-up, and the anti-HBs titer (> 10 mU / L ) Were intrauterine infection group, 71 cases; another healthy children a total of 40 peripheral blood as a control. The genomic DNA of peripheral blood was extracted and sequenced after PCR amplification. SNP of 3’UTR + 1188 (A / C) site in IL-12B gene was detected. Results The frequencies of AA, AC and CC genotypes at IL-12B +1188 in intrauterine infection group were 25.7%, 44.3% and 30.0%, respectively. The distribution frequency of intrauterine infection group was 36.6% and 47.9% And 15.5% respectively. The distribution frequencies of the three genotypes in the normal control group were 48.8%, 39.0% and 12.2% respectively. There were significant differences in the frequency distribution of CC genotypes and non-CC genotypes between intrauterine infection group and intrauterine infection group (X 2 = 17.078, P <0.01, OR cc = 2.338, 95% CI: 1.028 ~ 5.035). The frequencies of alleles in the three groups were A 47.8%, 60.7% and 67.8%, C 52.2%, 39.3% and 32.2%, respectively. The frequencies of alleles in intrauterine infection group and intrauterine uninfected group were The difference was statistically significant (X ~ 2 = 4.586, P = 0.032; OR_A = 0.597,95% CI: 0.372 ~ 0.959; OR_C = 1.673,95% CI: 1.043 ~ 2.684). Conclusions The intrauterine infection of HBV in CC genotype and C allele of IL-12B + 1188 polymorphism A / C polymorphism and C allele may be easy to occur in HBV intrauterine infection, but may occur in high risk infants born with HBV mothers HBV intrauterine infection has a protective effect.