Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis
Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis
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DOI：
10.1136/ard.2007.074948
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发表时间：
2008-08-01
影响因子：
27.4
通讯作者：
Padyukov, L.
中科院分区：
文献类型：
--
作者：
Kling, A.;Seddighzadeh, M.;Padyukov, L.
目的：为探讨HTR 2A基因多态性与类风湿性关节炎（RA）的关系，采用限制性内切酶酶谱分析和TaqMan等位基因识别技术，对4000多例RA患者和对照组进行了HTR 2A基因多态性分析。在发现阶段，我们发现RA患者和对照组之间rs6313（T102 C多态性）的频率存在显著差异（p = 0.006）。在用一组扩展的单核苷酸多态性（SNP）和DNA样本数进行验证后，SNP rs6314、rs 1328674、rs6313和rs6311的等位基因模型中的关联趋势（p = 0.006，0.002，0.006，0.009），尽管在对除rs 1328674外的所有数据进行多重比较校正后丢失（经验p值= 0.021）。然而，基于这四个SNP的单倍型频率分析显示，与对照组相比，RA患者中TCTT联合治疗的代表性显著降低（3.6%和5.6%，经卡方检验P < 0.001，100 000次置换后，经验p = 0.004），与对照组相比，RA患者CTCC联合治疗的频率显著更高（3.6%和2.2%，χ 2检验p = 0.002，100000次排列后经验p = 0.022）。结论：在我们的研究中，HTR 2A基因的遗传多态性与RA的易感性有关，提示β-羟色胺能系统与疾病的发展之间可能存在联系。
Objectives: To analyse the association between the genetic polymorphisms within the HTR2A gene for the serotonin receptor and rheumatoid arthritis (RA).Methods: HTR2A gene polymorphisms were analysed in patients with RA and controls from two study populations using PCR based restriction endonuclease mapping or TaqMan allelic discrimination with more than 4000 individuals included in the current study.Results: At the discovery stage we detected significant differences in frequency of rs6313 (T102C polymorphism) between the patients with RA and controls (p = 0.006). Following validation with an extended set of single nucleotide polymorphisms (SNPs) and number of DNA samples, a trend in associations in allelic model for SNPs rs6314, rs1328674, rs6313 and rs6311 (p = 0.006, 0.002, 0.006, 0.009) was seen, although it was lost after correction for multi-comparison for all but rs1328674 (empirical p value = 0.021). However, haplotype frequency analysis based on these four SNPs showed significantly low representation of TCTT combination in patients with RA in comparison with controls (3.6% and 5.6%, p < 0.001 on chi(2) test, empirical p = 0.004 after 100 000 permutations) and a significantly higher frequency of CTCC combination in patients with RA in comparison with controls (3.6% and 2.2%, p = 0.002 on chi(2) test, empirical p = 0.022 after 100 000 permutations).Conclusions: In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease.