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  • 郭心灵,尤崇革,王丽萍,马克君,周雅丽,施鑫鹤,李菲菲,郜莉娜.TNF-α及其受体基因多态性与类风湿性关节炎易感性和血清学指标相关性分析[J].第二军医大学学报,2012,33(2):155-159    [点击复制]
  • GUO Xin-ling,YOU Chong-ge,WANG Li-ping,MA Ke-jun,ZHOU Ya-li,SHI Xin-he,LI Fei-fei,GAO Li-na.Correlation analysis of gene polymorphisms of TNF-α and its receptors with rheumatoid arthritis susceptibility and related serological markers[J].Acad J Sec Mil Med Univ,2012,33(2):155-159   [点击复制]
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TNF-α及其受体基因多态性与类风湿性关节炎易感性和血清学指标相关性分析
郭心灵1,尤崇革1*,王丽萍2,马克君1,周雅丽1,施鑫鹤1,李菲菲1,郜莉娜3
0
(1.兰州大学第二医院中心实验室,兰州 730030
2.兰州大学第二医院风湿科,兰州 730030
3.兰州大学第二医院检验中心,兰州 730030
*通信作者)
摘要:
目的 探讨TNF-α及其受体基因多态性与中国西北地区汉族人群类风湿性关节炎(rheumatoid arthritis, RA)易感性及其血清学指标的相关性。方法 利用高分辨率熔解曲线(high resolution melting, HRM) 技术对452例RA患者和匹配的356例正常对照人群的TNF-α及其受体6个SNP位点(TNFA -857C>T、TNFA -863C>A、TNFA -308G>A、TNFA -238G>A、TNFR1-383A>C、TNFR2-exonT>G)的基因多态性进行病例-对照研究。此外,采用临床常规方法 测定RA患者的抗环瓜氨酸肽抗体(anti-CCP)和类风湿因子(RF),分析其与6个SNP位点的相关性。结果 TNFA -308GA和-863CA基因型在RA病例组和正常对照组中频率分布差异有统计学意义(P=0.001, P=0.002),TNFA -238GA、TNFA -238AA及TNFR2-exonTG、TNFR2-exonGG基因型在两组间频率分布差异无统计学意义(P=0.701,P=0.999,P=0.825,P=0.330)。由TNFA 3个位点构成的单倍型-238G/-308A/-863C(GAC)、-238G/-308G/-863A(GGA)和-238G/-308G/-863C(GGC)在两组间的频率分布差异均有统计学意义 (P=0.016,P=0.033,P=0.023)。TNF-α及其受体基因多态性与RA血清学指标(RF、anti-CCP)未见明显相关性。结论 TNFA -308GA和TNFA -863CA与中国西北地区汉族人群RA易感性相关;TNFA单倍型GAC、GGA和GGC与RA易感性相关;TNF-α及其受体基因多态性与RA患者血清学指标未见明显相关性。
关键词:  类风湿性关节炎  肿瘤坏死因子α  单核苷酸多态性  疾病易感性  血清学
DOI:10.3724/SP.J.1008.2012.0155
投稿时间:2011-09-08修订日期:2011-12-20
基金项目:甘肃省科技支撑计划(090NKC094).
Correlation analysis of gene polymorphisms of TNF-α and its receptors with rheumatoid arthritis susceptibility and related serological markers
GUO Xin-ling1,YOU Chong-ge1*,WANG Li-ping2,MA Ke-jun1,ZHOU Ya-li1,SHI Xin-he1,LI Fei-fei1,GAO Li-na3
(1. Central Laboratory, Lanzhou University Second Hospital, Lanzhou 730030, Gansu, China
2. Department of Rheumatism, Lanzhou University Second Hospital, Lanzhou 730030, Gansu, China
3. Clinical Laboratory Center, Lanzhou University Second Hospital, Lanzhou 730030, Gansu, China
*Corresponding author.)
Abstract:
Objective To investigate the correlation of gene polymorphisms of TNF-α and its receptor with rheumatoid arthritis (RA) susceptibility and the related serological markers in the Han nationality living in northwest China. MethodsThe gene polymorphisms of TNF-α and its receptor (TNFA -857C>T, TNFA -863C>A,TNFA -308G>A,TNFA -238G>A,TNFR1-383A>C,TNFR2-exonT>G) were determined by high resolution melting (HRM) in 452 RA patients and 356 controls in a case-control manner. Anti-cyclic citrullinated protein antibodies (anti-CCP) and rheumatoid factors (RF) were measured by clinical conventional methods, and their association with the gene polymorphisms of TNF-α and its receptor was analyzed. ResultsSignificant differences were found in the distribution frequencies of TNFA -308GA and -863CA between RA cases and healthy controls (P=0.001,P=0.002), but not in the frequencies of TNFA -238GA,TNFA -238AA,TNFR2-exonTG or TNFR2-exonGG (P=0.701,P=0.999,P=0.825, P=0.330). In addition, significant differences were also found in the distribution frequencies of TNFA haplotypes of -238G/-308A/-863C(GAC), -238G/-308G/-863A(GGA) and -238G/-308G/-863C(GGC) between the two groups (P=0.016, P=0.033, P=0.023). Furthermore, we found that RA serological markers (RF, anti-CCP) were not significantly correlated with the gene polymorphisms of TNF-α and its receptors. ConclusionTNFA -308GA and TNFA -863CA are associated with RA susceptibility in Han nationality living in northwest China, so are the TNFA haplotypes of GAC, GGA and GGC. Gene polymorphisms TNF-α and its receptor have no significant correlation with RA serological markers.
Key words:  rheumatoid arthritis  tumor necrosis factor-alpha  single nucleotide polymorphism