Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Liver Int. 2013 Aug;33(7):1039-43. doi: 10.1111/liv.12157. Epub 2013 Mar 31.
BACKGROUND & AIMS: Single nucleotide polymorphisms (SNP) in the Cytotoxic T lymphocyte antigen-4 gene (CTLA-4) have been associated with several autoimmune diseases including autoimmune Hepatitis (AIH). In this chronic idiopathic inflammatory liver disease, conflicting results have been reported on the association with a SNP at position +49 in the CTLA-4 gene in small patient cohorts. Here, we established the role of this SNP in a sufficiently large cohort of AIH patients.
The study population consisted of 672 AIH patients derived from academic and regional hospitals in the Netherlands and was compared with 500 controls selected from the 'Genome of the Netherlands' project cohort. Genotype frequencies were assessed by PCR for patients and by whole genome sequencing for controls.
No significant differences in allele frequencies were found between patients and controls (G Allele: 40% vs 39%, P = 0.7). Similarly, no significant differences in genotype frequencies between patients and controls were found. Finally, there was no relation between disease activity and the G allele or AG and GG genotypes.
The Cytotoxic T Lymphocyte Antigen-4 +49 A/G polymorphism does not represent a major susceptibility risk allele for AIH in Caucasians and is not associated with disease severity at presentation.
细胞毒性 T 淋巴细胞相关抗原 4 基因（CTLA-4）中的单核苷酸多态性（SNP）与多种自身免疫性疾病有关，包括自身免疫性肝炎（AIH）。在这种慢性特发性炎症性肝病中，关于 CTLA-4 基因第 +49 位 SNP 与疾病的相关性，在小患者队列中报告了相互矛盾的结果。在此，我们在足够大的 AIH 患者队列中确定了该 SNP 的作用。
研究人群包括来自荷兰学术和地区医院的 672 名 AIH 患者，并与来自“荷兰基因组”项目队列的 500 名对照进行比较。通过 PCR 对患者进行基因型频率评估，通过全基因组测序对对照进行评估。
患者和对照组之间等位基因频率无显著差异（G 等位基因：40%比 39%，P=0.7）。同样，患者和对照组之间基因型频率也无显著差异。最后，疾病活动与 G 等位基因或 AG 和 GG 基因型之间没有关系。
在高加索人群中，细胞毒性 T 淋巴细胞相关抗原 4 +49 A/G 多态性不是 AIH 的主要易感风险等位基因，也与发病时的疾病严重程度无关。
