白细胞介素-12B+1188位点基因多态性与乙型肝炎病毒宫内感染的关系  

Relationship between interleukin-12B gene + 1188 polymorphism and the susceptibility to hepatitis B virus intrauterine infection

作　　者：葛艳玲[1] 朱启镕[1] 王建设[1] 

机构地区：[1]复旦大学附属儿科医院传染科暨复旦大学小儿肝病中心,上海200032

出　　处：《中华传染病杂志》2007年第7期408-411,共4页Chinese Journal of Infectious Diseases

基　　金：国家自然科学基金(30271365)

摘　　要：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 Study the relationship between interleukin（IL）-12B gene 3＇ untranslating region （UTR） ＋ 1188 （A/C） single nucleotide polymorphism （SNP） and the susceptibility to hepatitis B virus（HBV） intrauterine infection and identify the genetic susceptible factors of intrauterine HBV infection in high-risk children. Methods The newborns whose mothers were HBV carriers [HBsAg and（or） HBeAg positive, or HBV DNA positive3 were immunized with hepatitis B vaccine and hepatitis B immunoglobulin（HBIG）. Those whose HBsAg and（or） HBV DNA positive in the peripheral blood at birth and lasting at least 6 months were identified as intrauterine HBV infection （Group Ⅰ , 70 cases）. None intrauterine HBV infection were defined that whose HBsAg and（or） HBV DNA were negative in the peripheral blood after birth and HBsAb titers level were 〉 10 mU/L （Group Ⅱ , 71 cases） when they were one year old. There were 40 healthy children in control group. The genomic DNA from the peripheral blood was extracted and polymerase chain reaction （PCR） and sequencing were employed to detect the IL-12B gene 3＇UTR ＋ 1188 SNP. Results The frequency of AA, AC and CC genotype in Group Ⅰ were 25.7%, 44.3% and 30.0%respectively, and 36.6%, 47.9% and 15.5% in Group Ⅱ , 48.8%, 39.0% , 12.2%, in control group, respectively. The difference of frequency of CC genotype and non-CC genotype between Group Ⅰ and Group Ⅱ was significant （X^2 = 17. 078, P 〈 0.01, ORcc = 2. 338, 95%CI：1. 028-5. 035） ; The frequency of IL-12B＋1188 alleles in three groups were A allele 47.8%, 60.7% and 67.8%, C allele 52.2%, 39.3% and 32.2%, respectively. There was significant difference of allele frequency between Group Ⅰ and Ⅱ （X^2 = 4. 586, P = 0. 032, ORA = 0. 597, 95%CI：0. 372-0. 959; ORc = 1. 673, 95%CI：1. 043-2. 684）. Conclusions A/C polymorphism genotype CC and C allele carriers of IL-12B＋ 1188 site may be susceptible to intrauterine HBV infection and A allele may protect high-risk infa

关 键 词：肝炎病毒 乙型 基因型 多态性 单核苷酸 白细胞介素12 疾病传播 垂直 等位基因 

分 类 号：R512.6[医药卫生—内科学] R714.2[医药卫生—临床医学]