Statistically significant results of an association analysis between SNPs of non-HLA genes and clinical baseline characteristics of patients

Analysis of the SNPs genotype frequencies and the initial clinical characteristics of the patients in our sample revealed associations for a number of genes and loci. However, when adjusting for multiple hypothesis testing, no significant associations were revealed. The table presents the loci and genes with significant associations with the initial clinical and biochemical parameters. The study of correlations of genotype frequencies with clinical characteristics and biochemical parameters of the patients revealed significant associations mainly for non-HLA genes. The HLA-B27 genotypes were significantly associated only with elevated anti-CCP level (p=0.008). While PADI4 [rs11203367, rs2240340, rs11203366, rs874881], AMPD1 [rs17602729], IL23R [rs10889671, rs11465770], IL4R [rs1801275], IL4 [rs2243250], IL6 [rs2069849] were significantly associated with the severity of the disease (DAS28, CDAI, HAQ-DI). MTHFR [rs180113] and DHODH [rs3213422] were associated with CRP level; IRAK3 [rs11541076], IL2RA [rs2104286], IL4R [rs1801275] were associated with the rheumatoid factor (RF) level and IL23R [rs7539625, rs7530511, rs10889671], IL2RB [rs3218253], IL6R [rs 2228144], STAT4 [rs7574865], TNFRSF1A [rs767455, rs1800693] are associated with anti-CCP level.

本研究对入组患者的单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs）基因型频率及初始临床特征进行分析后，发现多个基因与基因座存在关联。但经多重假设检验校正后，未检出具有统计学意义的关联。本表格列出了与患者初始临床及生化指标存在显著关联的基因座与基因。
对患者基因型频率与临床特征、生化指标的相关性分析显示，显著关联主要集中于非人类白细胞抗原（Human Leukocyte Antigen, HLA）基因。其中人类白细胞抗原B27（HLA-B27）基因型仅与抗环瓜氨酸肽抗体（anti-cyclic citrullinated peptide antibody, anti-CCP）水平升高存在显著关联（p=0.008）。
肽基精氨酸脱亚胺酶4（Peptidylarginine Deiminase Type 4, PADI4）[rs11203367、rs2240340、rs11203366、rs874881]、腺苷单磷酸脱氨酶1（Adenosine Monophosphate Deaminase 1, AMPD1）[rs17602729]、白细胞介素23受体（Interleukin 23 Receptor, IL23R）[rs10889671、rs11465770]、白细胞介素4受体（Interleukin 4 Receptor, IL4R）[rs1801275]、白细胞介素4（Interleukin 4, IL4）[rs2243250]、白细胞介素6（Interleukin 6, IL6）[rs2069849]均与疾病严重程度评分显著相关，具体包括疾病活动度评分28（Disease Activity Score 28, DAS28）、临床疾病活动指数（Clinical Disease Activity Index, CDAI）及健康评估问卷残疾指数（Health Assessment Questionnaire-Disability Index, HAQ-DI）。
亚甲基四氢叶酸还原酶（Methylenetetrahydrofolate Reductase, MTHFR）[rs180113]与二氢乳清酸脱氢酶（Dihydroorotate Dehydrogenase, DHODH）[rs3213422]与C反应蛋白（C-reactive protein, CRP）水平相关；白细胞介素1受体激酶3（Interleukin 1 Receptor-Associated Kinase 3, IRAK3）[rs11541076]、白细胞介素2受体α亚基（Interleukin 2 Receptor Subunit Alpha, IL2RA）[rs2104286]、白细胞介素4受体（IL4R）[rs1801275]与类风湿因子（Rheumatoid Factor, RF）水平相关；而白细胞介素23受体（IL23R）[rs7539625、rs7530511、rs10889671]、白细胞介素2受体β亚基（Interleukin 2 Receptor Subunit Beta, IL2RB）[rs3218253]、白细胞介素6受体（Interleukin 6 Receptor, IL6R）[rs2228144]、信号转导与转录激活因子4（Signal Transducer and Activator of Transcription 4, STAT4）[rs7574865]、肿瘤坏死因子受体超家族成员1A（Tumor Necrosis Factor Receptor Superfamily Member 1A, TNFRSF1A）[rs767455、rs1800693]均与抗环瓜氨酸肽抗体（anti-CCP）水平相关。