GAD2基因多型性與類風濕性關節炎病人之關係

Glutamate Decarboxylase 2 (GAD2) Gene Polymorphisms in Rheumatoid Arthritis Patients

目的：類風濕性關節炎是一種慢性自身免疫性疾病，根據以前的研究指出，它與許多基因的單核苷酸多型性有關，在我們先前的研究中，GAD2基因可能是其中一項，此研究的目的是找尋GAD2基因單核苷酸多型性與類風溼性關節炎的關聯。
方法：從高醫招募了186位類風濕性關節炎患者和151位健康對照者，並蒐集他們的實驗數據，包括類風濕因子、抗環瓜氨酸肽抗體、抗核抗體和抗Ro抗體，且以統計軟體做分析，並且我們以生物製劑的使用代表疾病的嚴重度與難治性，且用高血壓與糖尿病代表共病。
結果：類風濕性關節炎患者與健康組之間GAD2基因多型性盛行率沒有顯著差異。類風濕因子盛行率與單核苷酸多型性無關，然而GAD2基因中的rs8190582 A>T（p=0.02，顯性模型p=0.02）和rs2236418 A>G（p=0.05，顯性模型p=0.036），患者的抗環瓜氨酸肽抗體盛行率較低。而在抗核抗體部分，GAD2 rs2839670 C>A（p=0.023，隱性模型p=0.037）和rs2236418 A>G（p=0.03，隱性模型p=0.037）中，患者的抗核抗體盛行率較高；GAD2 rs8190582 A>T患者的抗Ro抗體盛行率較低（顯性模型p=0.02，等位基因頻率p=0.028）；而GAD2 rs2236418 A>G的患者則是有比較低抗Ro抗體盛行率的趨勢（顯性模型p=0.062，等位基因頻率p=0.054，GAD2基因多型性與生物製劑使用的盛行率沒有顯著相關。在類風濕關節炎患者比起健康組之間，高血壓盛行率有顯著較高(p<0.001)但糖尿病盛行率在兩組間無顯著差異，並且高血壓與糖尿病的盛行率和GAD2基因多型性沒有顯著相關性。
結論：GAD2基因單核苷酸多型性與類風溼性關節炎易感性無關，不過它與類風濕性關節炎患者的抗環瓜氨酸肽抗體、抗核抗體和抗Ro抗體的盛行率有關。

Objective: IRheumatoid arthritis (RA) is a chronic autoimmune disorder that is reported as being associated with single-nucleotide polymorphisms (SNP) of many genes. Our previous analysis determined that the glutamate decarboxylase 2 (GAD2) gene might be one of these; accordingly, our aim was to investigate the associations between GAD2 SNPs and RA.
Methods: 186 RA patients and 151 healthy controls were recruited from a single medical center. Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, antinuclear antibody (ANA), and anti-Ro antibody accounted for the analysis.
Results: There were no significant differences in the genotype and allele frequencies of GAD2 gene polymorphisms between rheumatoid arthritis patients and healthy controls while the prevalence of RF was not related to polymorphisms, although patients with GAD2 rs8190582 A>T (p=0.02 in genotype, p=0.02 in dominant model) and rs2236418 A>G (p=0.05 in genotype, p=0.036 in dominant model) had lower prevalence of anti-CCP antibody; patients with GAD2 rs2839670 C>A (p=0.023 in genotype, p=0.037 in recessive model) and rs2236418 A>G (p=0.03 in genotype, p=0.037 in recessive model) had higher prevalence of ANA; patients with GAD2 rs8190582 A>T had lower prevalence of anti-Ro antibody (p=0.02 in the dominant model, p=0.028 in allele frequency); and patients with GAD2 rs2236418 A>G tended to have lower prevalence of anti-Ro antibody (p=0.062 in the dominant model, p=0.054 in allele frequency).
Conclusions: GAD2 gene polymorphisms were not related to the susceptibility to RA, however, the polymorphisms of GAD2 were associated with the presence of anti-CCP antibody, ANA, and anti-Ro antibody in patients with RA.