Ben Kilani Mohamed Sahbi, Achour Yosser, Perea Javier, Cornelis François, Bardin Thomas, Chaudru Valérie, Maalej Abdellatif, Petit-Teixeira Elisabeth
GenHotel-EA3886, Evry University, 2 rue Gaston Cremieux, 91057, Evry-cedex, France.
Laboratory of Human Molecular Genetics, Sfax's Faculty of Medicine, Avenue Majida Boulila, 3029, Sfax, Tunisie.
Clin Rheumatol. 2016 Aug;35(8):1917-1922. doi: 10.1007/s10067-015-3156-y. Epub 2016 Jan 4.
Analyses of copy number variants (CNVs) for candidate genes in complex diseases are currently a promising research field. CNVs of C-C chemokine ligand 3-like 1 (CCL3L1) gene are candidate genomic factors in rheumatoid arthritis (RA). We investigated CCL3L1 CNVs association with a case-control study in Tunisians and a transmission analysis in French trio families. Relative copy number (rCN) of CCL3L1 gene was quantified by droplet digital PCR (ddPCR) in 100 French trio families (RA patients and their two parents) and in 166 RA cases and 102 healthy controls from Tunisia. We calculated odds ratio (OR) to investigate association risk for CCL3L1 CNVs in RA. rCN identified varied from 0 to 4 in the French population and from 0 to 7 in the Tunisian population. A significant difference was observed in the distribution of these rCNs between the two populations (p = 2.34 × 10(-10)), as when rCN from French and Tunisian RA patients were compared (p = 2.83 × 10(-5)). CNVs transmission in French RA trios allowed the characterization of genotypes with the presence of tandem duplication and triplication on the same chromosome. RA association tests highlighted a protective effect of rCN = 5 for CCL3L1 gene in the Tunisian population (OR = 0.056; CI 95 % [0.01-0.46]). Characterization of CCL3L1 CNVs with ddPCR methodology highlighted specific CN genotypes in a French family sample. A copy number polymorphism of a RA candidate gene was quantified, and its significant association with RA was revealed in a Tunisian sample.
对复杂疾病候选基因的拷贝数变异（CNV）分析目前是一个很有前景的研究领域。C-C趋化因子配体3样1（CCL3L1）基因的CNV是类风湿关节炎（RA）的候选基因组因素。我们通过对突尼斯人的病例对照研究和对法国家庭三人组的传递分析，研究了CCL3L1 CNV的相关性。采用液滴数字PCR（ddPCR）对100个法国家庭三人组（RA患者及其双亲）以及来自突尼斯的166例RA患者和102名健康对照者的CCL3L1基因相对拷贝数（rCN）进行定量。我们计算比值比（OR）以研究CCL3L1 CNV在RA中的关联风险。在法国人群中鉴定出的rCN范围为0至4，在突尼斯人群中为0至7。在这两个人群之间观察到这些rCN的分布存在显著差异（p = 2.34×10⁻¹⁰），法国和突尼斯RA患者的rCN比较时也是如此（p = 2.83×10⁻⁵）。对法国RA三人组的CNV传递分析使得能够对同一染色体上存在串联重复和三倍体的基因型进行特征描述。RA关联测试突出了rCN = 5对突尼斯人群中CCL3L1基因的保护作用（OR = 0.056；95%置信区间[0.01 - 0.46]）。采用ddPCR方法对CCL3L1 CNV进行特征描述突出了法国家庭样本中的特定CN基因型。对一个RA候选基因的拷贝数多态性进行了定量，并在突尼斯样本中揭示了其与RA的显著关联。
