Bos S D, Kloppenburg M, Suchiman E, van Beelen E, Slagboom P E, Meulenbelt I
Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.
Osteoarthritis Cartilage. 2009 May;17(5):621-6. doi: 10.1016/j.joca.2008.10.007. Epub 2008 Oct 25.
Investigating the association between plasma levels of cytokines and chemokines, Selenoprotein S (SELS) gene variation and osteoarthritis (OA) subtypes.
The genetics of osteoarthritis and progression (GARP) study consists of 191 sibling pairs with symptomatic OA at multiple joint sites. We have measured plasma levels of 17 cytokines and chemokines and genetic variation at the SELS gene.
Nine out of 17 serum markers could be assessed quantitatively, whereas eight markers were assessed qualitatively. Principal component analysis (PCA) on the quantitatively assessed markers and serum high sensitive C-reactive protein (S-HsCRP) revealed that three components underlie 61% of the total plasma variation. Three single nucleotide polymorphisms (SNPs) in the SELS gene revealed four common haplotypes, one of which, GAG (frequency 3.5%) showed significant association to an anti-inflammatory (P=0.019) and acute phase related (P=0.036) component. OA subtype analysis showed that one component (mainly representing chemokine variation) was significantly associated to hand OA and disc degeneration (P=0.029 and P=0.010 respectively) as well as a physical component score (PCS) (P=0.042). The CRP related component also showed a strong association to the PCS (P=0.007). SELS haplotypes showed no association to OA subtypes in the GARP study.
Genetic variation in the SELS gene associates to components representing inflammatory signaling. Another component, representing chemokine variation, showed association to hand OA and disc degeneration in the GARP study indicating chemokines may contribute to OA pathogenesis.
研究细胞因子和趋化因子的血浆水平、硒蛋白S（SELS）基因变异与骨关节炎（OA）亚型之间的关联。
骨关节炎与进展遗传学（GARP）研究由191对在多个关节部位患有症状性OA的同胞对组成。我们测量了17种细胞因子和趋化因子的血浆水平以及SELS基因的遗传变异。
17种血清标志物中有9种可以进行定量评估，而8种标志物进行定性评估。对定量评估的标志物和血清高敏C反应蛋白（S-HsCRP）进行主成分分析（PCA）显示，三个成分构成了血浆总变异的61%。SELS基因中的三个单核苷酸多态性（SNP）揭示了四种常见单倍型，其中一种，GAG（频率3.5%）与抗炎成分（P=0.019）和急性期相关成分（P=0.036）显示出显著关联。OA亚型分析表明，一个成分（主要代表趋化因子变异）与手部OA和椎间盘退变显著相关（分别为P=0.029和P=0.010）以及身体成分评分（PCS）（P=0.042）。CRP相关成分也与PCS显示出强关联（P=0.007）。在GARP研究中，SELS单倍型与OA亚型无关联。
SELS基因的遗传变异与代表炎症信号的成分相关。在GARP研究中，另一个代表趋化因子变异的成分与手部OA和椎间盘退变相关，表明趋化因子可能参与OA发病机制。
