Carlini Federico, Traore Karim, Cherouat Nissem, Roubertoux Pierre, Buhler Stéphane, Cortey Martì, Simon Sophie, Doumbo Ogobara, Chiaroni Jacques, Picard Christophe, Di Cristofaro Julie
Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, Bamako, Mali.
PLoS One. 2013 Dec 23;8(12):e82517. doi: 10.1371/journal.pone.0082517. eCollection 2013.
The HLA-G molecule plays an important role in immunomodulation. In a previous study carried out on a southern French population our team showed that HLA-G haplotypes, defined by SNPs in the coding region and specific SNPs located in 5'URR and 3'UTR regulatory regions, are associated with differential soluble HLA-G expression (sHLA-G). Furthermore, the structure of these HLA-G haplotypes appears to be conserved in geographically distant populations. The aim of our study is to confirm these expectations in a sub-Saharan African population and to explore additional factors, such as HLA-A alleles, that might influence sHLA-G expression. DNA and plasma samples were collected from 229 Malians; HLA-G and HLA-A genotyping were respectively performed by the Snap Shot® method and by Luminex™ technology. sHLA-G dosage was performed using an ELISA kit. HLA-G and HLA-A allelic and haplotypic frequencies were estimated using an EM algorithm from the Gene[Rate] program. Associations between genetic and non genetic parameters with sHLA-G were performed using a non-parametric test with GRAPH PAD Prism 5. Our results reveal a good conservation of the HLA-G UTR haplotype structure in populations with different origins and demographic histories. These UTR haplotypes appear to be involved in different sHLA-G expression patterns. Specifically, the UTR-2 haplotype was associated with low sHLA-G levels, displaying a dominant negative effect. Furthermore, an allelic effect of both HLA-G and HLA-A, as well as non genetic parameters, such as age and gender possibly linked to osteogenesis and sexual hormones, also seem to be involved in the modulation of sHLA-G. These data suggest that further investigation in larger cohorts and in populations from various ethnical backgrounds is necessary not only to detect new functional polymorphism in HLA-G regulatory regions, but also to reveal the extent of biological phenomena that influence sHLA-G secretion and this might therefore have an impact on transplantation practice.
HLA - G分子在免疫调节中发挥着重要作用。在之前对法国南部人群进行的一项研究中，我们的团队表明，由编码区单核苷酸多态性（SNP）以及位于5'非翻译调控区（5'URR）和3'非翻译调控区（3'UTR）的特定SNP所定义的HLA - G单倍型，与可溶性HLA - G（sHLA - G）的差异表达相关。此外，这些HLA - G单倍型的结构在地理上相距遥远的人群中似乎是保守的。我们研究的目的是在撒哈拉以南非洲人群中证实这些预期，并探索其他可能影响sHLA - G表达的因素，例如HLA - A等位基因。从229名马里人那里收集了DNA和血浆样本；分别通过Snap Shot®方法和Luminex™技术进行HLA - G和HLA - A基因分型。使用酶联免疫吸附测定（ELISA）试剂盒进行sHLA - G定量。使用来自Gene[Rate]程序的期望最大化（EM）算法估计HLA - G和HLA - A等位基因及单倍型频率。使用GRAPH PAD Prism 5软件进行非参数检验，分析遗传和非遗传参数与sHLA - G之间的关联。我们的结果显示，在具有不同起源和人口统计学历史的人群中，HLA - G非翻译区（UTR）单倍型结构具有良好的保守性。这些UTR单倍型似乎参与了不同的sHLA - G表达模式。具体而言，UTR - 2单倍型与低sHLA - G水平相关，表现出显性负效应。此外，HLA - G和HLA - A的等位基因效应，以及可能与成骨作用和性激素相关的年龄和性别等非遗传参数，似乎也参与了sHLA - G的调节。这些数据表明，有必要在更大的队列以及来自不同种族背景的人群中进行进一步研究，这不仅是为了检测HLA - G调控区新的功能多态性，也是为了揭示影响sHLA - G分泌的生物学现象的程度，因此这可能会对移植实践产生影响。
