胆盐输出泵基因V444A与特发性婴儿肝炎肝内胆汁淤积的关系

Association between BSEP V444A polymorphism and risk of idiopathic neonatal hepatitis/cholestasis

目的:探讨胆盐输出泵BSEP基因V444A(BSEPV444A)与特发性婴儿肝炎肝内胆汁淤积的相关性.方法:以81例特发性婴儿肝炎肝内胆汁淤积患儿(病例组)和48例无肝内胆汁淤积婴儿(对照组)为研究对象,应用聚合酶链-限制性片段长度多态性(PCR-RFLP)技术对V444A片段行扩增及酶切分析.结果:BSEPV444A有3种基因型:AA纯合子、GA杂合子、GG纯合子,AA,AG和GG3种基因型在病例组和对照组频率分别为4.9%,50.6%,44.4%和14.6%,62.5%,22.9%,两组差异显著(P=0.019).等位基因频率的相对风险分析发现,其中GG基因型在两组人群中的分布差异有显著性(P<0.05,OR=2.691,95%CI:1.205-6.008);G等位基因携带者患特发性婴儿肝炎肝内胆汁淤积的风险是A等位基因的1.951倍(OR=1.951,95%CI:1.56-3.291).结论:在广西地区小儿当中发现BSEPV444A单链核苷酸的多态性位点,BSEPV444AG等位基因可能是特发性婴儿肝炎肝内胆汁淤积的一个危险因素,G等位基因携带者可能增加特发性婴儿肝炎肝内胆汁淤积的相对危险度.

AIM： To explore the association between the V444A polymorphism in the bile salt export pump （BSEP） gene and the risk of idiopathic neonatal hepatitis/cholestasis. METHODS： Eighty-one infants with idiopathic hepatitis/cholestasis （case group） and 48 healthy infants without intrahepatic cholestasis （control group） were included in this study. The V444A polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. RESULTS： There are three V444A genotypes： AA homozygote, GA heterozygote, and GG ho- mozygote. The frequencies of AA and AG and GG genotypes were 0.6%, 4.9% and 44.4% in the case group and 14.6%, 62.5% and 22.9% in the control group, respectively, with a significant difference between the two groups （P = 0.019）. The distribution of GG genotype was significantly different between the two groups （P 0.05, OR = 2.691, 95%CI： 1.205-6.008）. The risk of suffering from idiopathic intrahepatic cholestasis in G allele carriers was 1.951 times higher than that in A allele carriers （OR = 1.951, 95%CI： 1.56-3.291）. CONCLUSION： The G allele of the BSEP V444A G polymorphism may be a risk factor for idiopathic intrahepatic cholestasis in infants.