Chaouali Marwa, Carvalho Agostinho, Tezeghdenti Aymen, Ben Azaiez Mouna, Cunha Cristina, Ghazouani Ezzeddine, Kochkar Radhia
Department of Immunology, Military Hospital of Tunis, Montfleury 1008, Tunis, Tunisia.
El Manar University, Laboratory of Mycology, Pathologies and Biomarkers 1092, Tunis, Tunisia.
Genes Dis. 2017 Dec 30;5(3):256-262. doi: 10.1016/j.gendis.2017.12.006. eCollection 2018 Sep.
Genetic factors and gene polymorphisms leading to the onset of autoimmune response in autoimmune hepatitis (AIH) are still not full elucidated. Since the CTLA-4 molecule is a key modulator of the lymphocytes responses we hypothezied that deficiencies or mutations in the gene encoding CTLA4 protein may be involved in AIH susceptibility and trigger the autoimmune response. We investigated 3 distinct polymorphic sites (+49A > G, CT60 G > A and -318C > T) of the CTLA4 gene in 50 AIH patients and 100 healthy controls using the KASP genotyping technology. A significant positive association with AIH susceptibility was found for the GG genotype in +49 position of the CTLA4 gene which was significantly higher in AIH patients compared to controls (28% vs 9%, = 0.003, OR = 3.93 [1.56-9.88]). The CTLA4 A/A genotype in position CT60 was more significantly frequent in controls comparing to AIH patients and could be considered as a protective genotype for the tunisian patients. CTLA4 genotyping in position -318 did not show any statistically significant difference in genotype or allele distribution. The CTLA4 gene polymorphism in position +49 is associated to AIH susceptibility in the Tunisian population. Mutation in the CTLA4 gene may lead to a modification of the CTLA4 protein structure that could have functional relevance in AIH pathogenesis and onset.
导致自身免疫性肝炎（AIH）自身免疫反应发作的遗传因素和基因多态性仍未完全阐明。由于细胞毒性T淋巴细胞相关抗原4（CTLA-4）分子是淋巴细胞反应的关键调节因子，我们推测编码CTLA4蛋白的基因中的缺陷或突变可能与AIH易感性有关，并引发自身免疫反应。我们使用竞争性等位基因特异性PCR（KASP）基因分型技术，研究了50例AIH患者和100例健康对照者中CTLA4基因的3个不同多态性位点（+49A>G、CT60 G>A和-318C>T）。发现CTLA4基因+49位点的GG基因型与AIH易感性呈显著正相关，AIH患者中该基因型显著高于对照组（28%对9%，P=0.003，比值比[OR]=3.93[1.56-9.88]）。与AIH患者相比，CT60位点的CTLA4 A/A基因型在对照组中更为常见，可被视为突尼斯患者的一种保护性基因型。-318位点的CTLA4基因分型在基因型或等位基因分布上未显示任何统计学显著差异。CTLA4基因+49位点的多态性与突尼斯人群的AIH易感性相关。CTLA4基因的突变可能导致CTLA4蛋白结构的改变，这可能与AIH的发病机制和发病具有功能相关性。
