巨细胞病毒肝炎患儿IL-12p40 3′非翻译区基因多态性研究

Study on the Gene Polymorphism of IL-12p40 3′ Untranslated Region in Infant with Cytomegalovirus Hepatitis

目的研究巨细胞病毒（CMV）肝炎患儿IL-12p403＇非翻译区rs3212227位点的基因型分布，探讨该位点的单核苷酸多态性与婴儿CMV肝炎发生的关系。方法应用聚合酶链反应一限制性片段长度多态性（PCR—RFLP）技术和基因测序方法测定105例健康儿童及122例CMV肝炎患儿IL-12p403＇非翻译区rs3212227位点基因型，采用双抗体夹心ELISA法、速率法和实时荧光定量聚合酶链反应（FQ—PCIR）分别测定CMV肝炎患儿血清IL-12p40水平、ALT活性及尿HCMVDNA载量。结果CNV肝炎组IL-12p40rs3212227位点AA、AC、CC基因型分布频率分别为34．4％、41．8％、23．8％，正常对照组分另q为47．6％、40．0％、12．4％，两组间cc基因型和非cc基因型之间频率分布差异有统计学意义（x2=4．855，P〈0．05，ORcc=2．207，95％cI：1．080～4．510）。CMV肝炎组IL一12p40rs3212227位点等位基因A、c分布频率分别55．3％、44．7％，对照组分别为67．6％、32．4％，两组等位基因频率比较差异有统计学意义（x2=7．168，P〈0．01；ORA=0．593，95％CI：0．404～0．871；ORc：1．686，95％CI：1．149—2．475）。rs3212227位点不同基因型的CMV肝炎患儿之间血清IL-12p40水平、尿HCMVDNA载量（拷贝／毫升，lg）差异均有统计学意义（H=7．385、F=9．325，P均〈0．05），CC基因型患儿血清IL-12p40水平低于AA基因型，尿液HcMVDNA载量高于AA基因型，不剐基因型患儿之间血清ALT活性差异无统计学意义（P〉0．05）。结论IL—12p403’非翻译区rs3212227位点单核苷酸多态性与婴儿cMV肝炎的发生具有相关性，其中c等位基因可能是其遗传易感基因，携带c等位基因的个体可能更利于cMV病毒的复制。

Objective To investigate the single nucleotide polymorphism （SNP） of IL-12p403＇ untranslated region （3＇ UTR） rs3212227 site in cytomegalovirus hepatitis infants,and find the association between IL - 12p40 SNP and cytomegalovirus hepatitis in Chi- na. Methods We genotyped IL - 12p40 rs3212227 SNP of 122 cytomegalovirus hepatitis infants and 105 healthy controls by PCR - RFLP. We also detected IL- 12p40 level, ALT activity in serum and HCMV DNA in urinary of cytomegalovirus hepatitis infants. Results The frequency of AA,AC and CC genotype of IL - 12p40 rs3212227 site were 34.4% ,41.8% and 23.8% in CMV hepatitis infants, and the frequency were 47.6% ,40.0% and 12.4% in control group. And there was significant difference in CC genotype and non -CC genotype frequency between the two grouops （X2 = 4. 855, P 〈 O. 05, ORcc = 2. 207,95 % CI ： 1. 080 - 4.510）. The frequency of A, C allele of IL- 12p40 rs3212227 site were 55.3% ,44.7% in CMV hepatitis infants,and were 67.6% ,32.4% in control group. A significant difference was found in allele frequency distribution of IL -12p40 rs3212227 between the two groups （X2 = 7. 168, P 〈 0. O1 ;ORA = 0. 593, 95% CI：0.404 ~ 0. 871 ; ORc = 1. 686,95% CI：I. 149 ~ 2. 475）. There were signineant differences in HCMV DNA in urinary,IL - 12p40 level in serum between AA, AC and CC genotype of CMV hepatitis infants （ P 〈 0.05 ） , but there was no significant difference in ALT activity between the three genotype of CMV hepatitis infants. Conclusion There was a relationship between the SNP of IL - 121340 3＇ UTR rs3212227 and the susceptibility to CMV hepatitis in infants. The infants with C allele and CC genotype are susceptible to develop CMV infection.