Analysis of neuropeptide S receptor gene (NPSR1) polymorphism in rheumatoid arthritis.
Analysis of neuropeptide S receptor gene (NPSR1) polymorphism in rheumatoid arthritis.
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DOI：
10.1371/journal.pone.0009315
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发表时间：
2010-02-22
期刊：
影响因子：
3.7
通讯作者：
Padyukov L
中科院分区：
文献类型：
--
作者：
D'Amato M;Zucchelli M;Seddighzadeh M;Anedda F;Lindblad S;Kere J;Alfredsson L;Klareskog L;Padyukov L
神经肽S受体基因NPSR 1多态性与哮喘和炎症性肠病相关NPSR 1在大脑中表达，在那里它调节焦虑和对压力的反应，但也在其他组织和细胞类型中表达，包括淋巴细胞，肺和肠，在那里它似乎在炎症中上调。我们试图确定NPSR 1基因座的遗传变异是否影响类风湿关节炎（RA）的易感性和临床表现。在风湿性关节炎流行病学调查（EIRA）病例对照研究中，对1，888例类风湿性关节炎患者和888例对照进行了19个单核苷酸多态性（SNP）基因分型，这些SNP跨越整个NPSR 1基因和染色体7 p14上的220 KB DNA。检测了个体遗传标记及其单倍型组合分别与RA诊断、瓜氨酸化蛋白自身抗体（ACPA）的存在以及基于28个关节的疾病活动性评分（DAS 28）之间的相关性。RA的诊断与NPSR 1变异之间没有关联。然而，在ACPA阴性RA的易感性和疾病活动性测量（DAS 28）方面，检测到了几种名义上显著的相关性。其中，SNP rs324987与ACPA阴性RA的相关性[（p = 0.004，OR = 0.674（95%CI 0.512-0.888）]和SNP rs 10263447与DAS 28的相关性[p = 0.0002，OR = 0.380（95%CI 0.227-0.635）]在多重比较校正后仍然显著。 NPSR 1基因多态性可能与RA的易感性及临床表现有关。NPSR 1基因座的特定等位基因可能代表慢性炎症性疾病（包括RA）的常见风险因素。
Polymorphism in the neuropeptide S receptor gene NPSR1 is associated with asthma and inflammatory bowel disease. NPSR1 is expressed in the brain, where it modulates anxiety and responses to stress, but also in other tissues and cell types including lymphocytes, the lungs, and the intestine, where it appears to be up-regulated in inflammation. We sought to determine whether genetic variability at the NPSR1 locus influences the susceptibility and clinical manifestation of rheumatoid arthritis (RA). From the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) case-control study, 1,888 rheumatoid arthritis patients and 888 controls were genotyped for 19 single-nucleotide polymorphisms (SNPs) spanning the entire NPSR1 gene and 220 KB of DNA on chromosome 7p14. The association between individual genetic markers and their haplotypic combinations, respectively, and diagnosis of RA, presence of autoantibodies to citrullinated proteins (ACPA), and disease activity score based on 28 joints (DAS28) was tested. There was no association between diagnosis of RA and NPSR1 variants. However, several associations of nominal significance were detected concerning susceptibility to ACPA-negative RA and disease activity measures (DAS28). Among these, the association of SNP rs324987 with ACPA-negative RA [(p = 0.004, OR = 0.674 (95% CI 0.512–0.888)] and that of SNP rs10263447 with DAS28 [p = 0.0002, OR = 0.380 (95% CI 0.227–0.635)] remained significant after correction for multiple comparisons. NPSR1 polymorphism may be relevant to RA susceptibility and its clinical manifestation. Specific alleles at the NPSR1 locus may represent common risk factors for chronic inflammatory diseases, including RA.
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