Achour Y, Kammoun A, Ben Hamad M, Mahfoudh N, Chaabane S, Marzouk S, Keskes L, Gaddour L, Bahloul Z, Maalej A
Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Sfax, Tunisia.
Int J Immunogenet. 2014 Dec;41(6):486-92. doi: 10.1111/iji.12146. Epub 2014 Sep 26.
The aim of this study was to investigate the role of major histocompatibility complex (MHC) class I chain-related gene A (MICA) polymorphisms, important in natural killer (NK) cell function, in patients with rheumatoid arthritis (RA). A transmembrane (TM) alanine-encoding GCT repeats, termed A4, A5, A5.1, A6 and A9 in the MICA gene, and single-nucleotide polymorphisms (SNPs): the Met129Val polymorphism (rs1051792) and the nonsynonymously coding SNP (rs1051794) were genotyped in 142 patients with RA and 123 unrelated healthy individuals using, respectively, PCR fluorescent method, nested PCR-RFLP and allele specific PCR (ASP). Association was assessed based on the χ2 test, genotype relative risk (GRR) and odds ratio (OR) with 95% confidence intervals (CIs). Our results show a trend of association of the different MICA genotypes G/G, G/A and A/A (P = 0.029) which did not attain the significance after Bonferroni's correction (pc = 0.08). Although, we revealed a significant association of the genotype A/A of MICA-250 in patients with RA compared to healthy controls (pc = 0.033). In contrast, no significant differences between alleles and genotypes frequencies were found either with MICA-TM or MICA met129 val (P > 0.05) in our sample. Moreover, stratification of patients with RA according to clinical and immunological data for the different polymorphisms studied shows a significant association of both MICA-250 G allele (pc = 0.0075) and MICA-250 GG genotype (pc = 0.008) and both allelic (val) (pc = 0.021) and genotypic (val/val) distribution (pc = 0.0095) for MICA met129 val in the RF-positive subgroup compared to RF-negative patients with RA. In contrast, we found a strong association of the MICA-TM A9 allele in RF-negative patients with RA (pc = 0.0003). This study indicates the involvement of the MICA-250 polymorphism in the genetic susceptibility and severity to RA and suggests that variations in MICA-TM and MICA met129 val may have an effect on RA severity in our south Tunisian sample.
本研究旨在调查主要组织相容性复合体（MHC）I类链相关基因A（MICA）多态性在类风湿关节炎（RA）患者中的作用，该多态性在自然杀伤（NK）细胞功能中起重要作用。使用PCR荧光法、巢式PCR-RFLP和等位基因特异性PCR（ASP）分别对142例RA患者和123名无关健康个体的MICA基因中编码丙氨酸的跨膜（TM）GCT重复序列（称为A4、A5、A5.1、A6和A9）以及单核苷酸多态性（SNP）：Met129Val多态性（rs1051792）和非同义编码SNP（rs1051794）进行基因分型。基于χ2检验、基因型相对风险（GRR）和95%置信区间（CI）的优势比（OR）评估关联性。我们的结果显示不同MICA基因型G/G、G/A和A/A存在关联趋势（P = 0.029），经Bonferroni校正后未达到显著水平（pc = 0.08）。尽管如此，与健康对照相比，我们发现RA患者中MICA - 250的A/A基因型存在显著关联（pc = 0.033）。相反，在我们的样本中，MICA - TM或MICA met129 val的等位基因和基因型频率之间未发现显著差异（P > 0.05）。此外，根据所研究的不同多态性的临床和免疫学数据对RA患者进行分层分析显示，与RF阴性的RA患者相比，RF阳性亚组中MICA - 250的G等位基因（pc = 0.0075）和MICA - 250的GG基因型（pc = 0.008）以及MICA met129 val的等位基因（val）（pc = 0.021）和基因型（val/val）分布（pc = 0.0095）均存在显著关联。相反，我们发现RF阴性的RA患者中MICA - TM的A9等位基因存在强关联（pc = 0.0003）。本研究表明MICA - 250多态性与RA的遗传易感性和严重程度有关，并提示在我们突尼斯南部样本中，MICA - TM和MICA met129 val的变异可能对RA严重程度有影响。
