Li Y, Wang Y, He Y, Wang D, Deng L, Du Y, Shi G
State Key Laboratory of Biotherapy, Division of Rheumatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Genet Mol Res. 2013 Jun 11;12(2):1841-8. doi: 10.4238/2013.January.4.6.
Mice that lose Gαq from their immune system can spontaneously develop inflammatory arthritis. Gαq expression in the peripheral blood lymphocytes of rheumatoid arthritis (RA) patients is significantly decreased in comparison to that in healthy individuals, and reduced Gαq expression is closely correlated with RA disease activity. These indicate that Gαq plays critical roles in the pathogenesis of RA. To address whether single nucleotide polymorphism in the promoter region of the Gαq gene (GNAQ) influenced Gαq expression in RA patients and was a genetic risk factor for RA, we sequenced the promoter region of GNAQ in a Han Chinese population. A common dinucleotide polymorphism at position -695/-694, an exchange of 2 adjacent nucleotides (GC>TT), was revealed in 118 RA patients and 101 healthy adults. The proportions of genotypes observed for -695/-694 in the RA group were GC/GC (65.25%), GC/TT (33.05%), and TT/TT (1.70%), and those in the control group were GC/GC (62.38%), GC/TT (33.66%), and TT/TT (3.96%). No significant difference in the allele and genotype frequencies between RA patients and healthy controls for dinucleotide polymorphism was found in the Han Chinese population, neither in the whole data set nor in stratified subsets, i.e., rheumatoid factors, anti-cyclic citrullinated peptide antibody, and Gαq expression status (P > 0.05). We conclude that the GNAQ promoter polymorphism is not a genetic risk factor for RA in the Han Chinese population, and that decreased Gαq expression in peripheral blood lymphocytes of RA might potentially be due to other causes.
免疫系统中缺失Gαq的小鼠会自发患上炎性关节炎。与健康个体相比，类风湿关节炎（RA）患者外周血淋巴细胞中的Gαq表达显著降低，且Gαq表达降低与RA疾病活动密切相关。这些表明Gαq在RA发病机制中起关键作用。为了探究Gαq基因（GNAQ）启动子区域的单核苷酸多态性是否影响RA患者的Gαq表达以及是否是RA的遗传危险因素，我们对汉族人群的GNAQ启动子区域进行了测序。在118例RA患者和101例健康成年人中发现了位于-695/-694位置的一种常见二核苷酸多态性，即2个相邻核苷酸的交换（GC>TT）。RA组中-695/-694基因型的比例为GC/GC（65.25%）、GC/TT（33.05%）和TT/TT（1.70%），对照组中分别为GC/GC（62.38%）、GC/TT（33.66%）和TT/TT（3.96%）。在汉族人群中，无论是在整个数据集中还是在分层亚组（即类风湿因子、抗环瓜氨酸肽抗体和Gαq表达状态）中，RA患者和健康对照之间二核苷酸多态性的等位基因和基因型频率均未发现显著差异（P>0.05）。我们得出结论，GNAQ启动子多态性不是汉族人群RA的遗传危险因素，RA患者外周血淋巴细胞中Gαq表达降低可能是由其他原因引起的。
