Sookoian Silvia, Castaño Gustavo, Burgueño Adriana, Gianotti Tomas Fernández, Pirola Carlos J
Instituto de Investigaciones Medicas A. Lanari, Departamento de Genetica y Biología Molecular de Enfermedades Complejas, Universidad de Buenos Aires, CONICET, Combatientes de Malvinas 3150, Buenos Aires 1427, Argentina.
J Hepatol. 2008 Jan;48(1):125-32. doi: 10.1016/j.jhep.2007.08.015. Epub 2007 Oct 23.
BACKGROUND/AIMS: We hypothesized that common genetic variation at ABCC2 influences ICP susceptibility. Hence we studied the association of single nucleotide polymorphisms (SNPs) of promoter, coding and non-coding regions of ABCC2 and intrahepatic cholestasis of pregnancy (ICP).
70 ICP patients and 112 healthy pregnant women in the third trimester of their pregnancies were included in a cross sectional study. Four tag SNPs (rs717620 A/G; rs2756105 C/T; rs2002042 C/T; rs3740066 A/G) encompassing 70 kb in chr.10 and representing 46 polymorphic sites (r(2) > 0.8) were genotyped. Besides, 2 additional SNPs (rs17222723 A/T and rs8187710 G/A) were included.
In univariate analysis, rs2002042 and rs3740066 were significantly associated with ICP (p < 0.04 and 0.01, respectively) but after multiple testing correction, only rs3740066 remained significantly associated with disease status (p < 0.03). We also observed a positive association between the rs3740066 and ALT, AST, alkaline phosphatase and total and conjugated bilirubin concentrations. Consistent with the analysis of individual markers, we observed that haplotype frequency of the ABCC2 gene in ICP patients significantly differed from controls (p < 0.03).
We found an association between the rs3740066 in exon 28 of ABCC2 gene and ICP. The risk of disease for homozygous AA carriers is 4-fold higher (OR 4.44 CI 95% 1.83-10.78, p < 0.001) in comparison with GG carriers.
背景/目的：我们推测ABCC2基因的常见遗传变异会影响妊娠期肝内胆汁淤积症（ICP）的易感性。因此，我们研究了ABCC2基因启动子、编码区和非编码区的单核苷酸多态性（SNP）与妊娠期肝内胆汁淤积症（ICP）之间的关联。
一项横断面研究纳入了70例ICP患者和112例妊娠晚期健康孕妇。对位于10号染色体上、涵盖70kb且代表46个多态性位点（r²>0.8）的4个标签SNP（rs717620 A/G；rs2756105 C/T；rs2002042 C/T；rs3740066 A/G）进行基因分型。此外，还纳入了另外2个SNP（rs17222723 A/T和rs8187710 G/A）。
在单因素分析中，rs2002042和rs3740066与ICP显著相关（p分别<0.04和0.01），但经过多重检验校正后，只有rs3740066仍与疾病状态显著相关（p<0.03）。我们还观察到rs3740066与丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶以及总胆红素和结合胆红素浓度呈正相关。与单个标记物分析一致，我们观察到ICP患者中ABCC2基因的单倍型频率与对照组有显著差异（p<0.03）。
我们发现ABCC2基因第28外显子中的rs3740066与ICP之间存在关联。与GG携带者相比，纯合子AA携带者的疾病风险高4倍（比值比4.44，95%置信区间1.83 - 10.78，p<0.001）。
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