Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2010 Feb 22;5(2):e9315. doi: 10.1371/journal.pone.0009315.
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).
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: 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.
神经肽 S 受体基因 NPSR1 的多态性与哮喘和炎症性肠病有关。NPSR1 在大脑中表达，调节焦虑和应激反应，但也在其他组织和细胞类型中表达，包括淋巴细胞、肺和肠道，在炎症中似乎上调。我们试图确定 NPSR1 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。
方法/主要发现：从类风湿关节炎的流行病学调查（EIRA）病例对照研究中，对 1888 名类风湿关节炎患者和 888 名对照进行了 19 个单核苷酸多态性（SNP）的基因分型，这些 SNP 跨越整个 NPSR1 基因和 7p14 染色体上的 220KB DNA。分别测试了个体遗传标记及其单倍型组合与 RA 诊断、瓜氨酸蛋白自身抗体（ACPA）的存在以及基于 28 个关节的疾病活动评分（DAS28）之间的关联。NPSR1 变体与 RA 诊断之间没有关联。然而，在对 ACPA 阴性 RA 和疾病活动指标（DAS28）的易感性方面，检测到了几个具有名义意义的关联。其中，SNP rs324987 与 ACPA 阴性 RA 的关联[（p=0.004，OR=0.674（95%CI 0.512-0.888）]和 SNP rs10263447 与 DAS28 的关联[（p=0.0002，OR=0.380（95%CI 0.227-0.635）]在进行多重比较校正后仍然具有统计学意义。
结论/意义：NPSR1 多态性可能与 RA 的易感性及其临床表现有关。NPSR1 基因座的特定等位基因可能是包括 RA 在内的慢性炎症性疾病的常见危险因素。
